Methionine residues within the kinase domain of Src serve as unique NMR probes capable of distinguishing between distinct conformational states of full-length Src, including alternative drug-inhibited forms. This approach offers a rapid method to differentiate between various inhibition mechanisms at any stage of drug development, eliminating the need to resolve the structure of Src-drug complexes. Using selectively C-methyl-enriched methionine, spectra can be acquired in under an hour, while natural abundance spectra with comparable information are achievable within a few hours.
View Article and Find Full Text PDFMaterial Extrusion (MEX) currently stands as the most widespread Additive Manufacturing (AM) process, but part quality deficiencies remain a barrier to its generalized industrial adoption. Quality control in MEX is a complex task as extrusion performance impacts the consistency of mechanical properties and the surface finish, dimensional accuracy, and geometric precision of manufactured parts. Recognizing the need for early-stage process monitoring, this study explores the potential of integrating Laser Triangulation Sensors (LTS) into MEX/P manufacturing equipment for layer-wise 3D inspections.
View Article and Find Full Text PDFUnlabelled: The Swan Ganz Catheter (SGC) allows us to diagnose different types of cardiogenic shock (CS).
Objectives: 1) Determine the frequency of use of SGC, 2) Analyze the clinical characteristics and mortality according to its use and 3) Analyze the prevalence, clinical characteristics and mortality according to the type of Shock.
Methods: The 114 patients (p) from the ARGEN SHOCK registry were analyzed.
Life (Basel)
August 2023
Clonal hematopoiesis of indeterminate potential (CHIP) is defined by the clonal expansion of hematopoietic stem cells carrying certain genes associated with an increased risk of hematological malignancies. Our study analyzes the influence of CHIP on the risk of heart disease and cardiovascular events in a population with chronic kidney disease (CKD). A total of 128 patients were prospectively followed up for 18 months to detect major cardiovascular events (MACE).
View Article and Find Full Text PDFIn contrast to the well-studied canonical regulatory mechanisms, the way by which the recently discovered Src N-terminal regulatory element (SNRE) modulates Src activity is not yet well understood. Phosphorylation of serine and threonine residues modulates the charge distribution along the disordered region of the SNRE and may affect a fuzzy complex with the SH3 domain that is believed to act as an information transduction element. The pre-existing positively charged sites can interact with the newly introduced phosphate groups by modulating their acidity, introducing local conformational restrictions, or by coupling various phosphosites into a functional unit.
View Article and Find Full Text PDFAim: to assess if the use of an audiovisual intervention in the uptake room and/or in the scanning room, could help to reduce anxiety during [18F]FDG PET/CT imaging.
Methods: We prospectively studied 120 patients referred for [18F]FDG PET/CT imaging. Patients were allocated in 4 groups of 30 patients depending on the use of the audiovisual intervention: (1) no audiovisual intervention; (2) audiovisual intervention only in the uptake room; (3) audiovisual intervention only in the scanning room; (4) audiovisual intervention in the uptake and the scanning rooms.
High thrombus burden in ST segment elevation myocardial infarction (STEMI) patients increases the risk of adverse events. In this report, we review current strategies for high thrombus burden and present a case report with the combination of two different techniques: aspiration through a guide extension catheter followed by local intracoronary thrombolysis with 'marinade' technique.
View Article and Find Full Text PDFPurpose: To evaluate the reduction in the absorbed dose delivered to the neurovascular bundle (NB) in patients with localized prostate cancer treated with only HDR brachytherapy and NB protection with hyaluronic acid (HA) on the side of the prostate to increase the distance from NB to the radioactive sources.
Methods: This is the first published report in the medical literature that studies a new approach to decrease neurovascular bundle toxicity and improve quality of life for patients with prostate cancer treated with radical brachytherapy as monotherapy. Transperineal HA injection on the side of the prostate into the lateral aspect of the prostate fat was used to consistently displace several autonomic fibers and vessels on the lateral wall of the prostate away from radiation sources.
Uncertainty about the influence of anthropogenic radiative forcing on the position and strength of convective rainfall in the Intertropical Convergence Zone (ITCZ) inhibits our ability to project future tropical hydroclimate change in a warmer world. Paleoclimatic and modeling data inform on the timescales and mechanisms of ITCZ variability; yet a comprehensive, long-term perspective remains elusive. Here, we quantify the evolution of neotropical hydroclimate over the preindustrial past millennium (850 to 1850 CE) using a synthesis of 48 paleo-records, accounting for uncertainties in paleo-archive age models.
View Article and Find Full Text PDFIn signaling proteins, intrinsically disordered regions often represent regulatory elements, which are sensitive to environmental effects, ligand binding, and post-translational modifications. The conformational space sampled by disordered regions can be affected by environmental stimuli and these changes trigger, vis a vis effector domain, downstream processes. The disordered nature of these regulatory elements enables signal integration and graded responses but prevents the application of classical approaches for drug screening based on the existence of a fixed three-dimensional structure.
View Article and Find Full Text PDFIntroduction: Neutralizing antibodies to coagulation factor VIII (FVIII) remain a major complication associated with FVIII replacement therapy.
Aim: To assess safety and efficacy of immune tolerance induction (ITI) therapy with ADVATE (antihemophilic factor [recombinant] [rAHF]) in patients who participated in the Prospective ADVATE Immune Tolerance Induction Registry (PAIR) study.
Methods: The PAIR study was an international, multicenter, open-label, prospective, observational study in patients with hemophilia A and inhibitors, prescribed rAHF ITI therapy in clinical practice.
Purpose: Skeletal muscle mass (SMM) loss and sarcopenia have been identified as risk factors for postoperative complications. The aim of this study was to investigate the relationship between pharyngocutaneous fistula (PCF) formation after total laryngectomy (TL) and SMM assessed from a computed tomography image of the 3rd cervical vertebra (C3).
Methods: Retrospective study of 86 male patients who underwent TL between 2013 and 2019 in a single institution.
Bioprinting technology offers layer-by-layer positioning of cells within 3D space with complexity and a defined architecture. Cancer models based in this biofabrication technique are important tools to achieve representative and realistic in vivo conditions of the tumor microenvironment. Here, we show the development of a proof-of-concept three-dimensional bioprinted cancer model that successfully recapitulates the intercellular communication via the assembly of functional tunneling nanotube (TNT)-like cell projections.
View Article and Find Full Text PDFBackground And Aims: intraoperative identification of colonic lesions previously detected via colonoscopy may be difficult. Endoscopic tattooing facilitates identification, but there is no evidence regarding which is the best tattoo technique. The goal of the study was to describe the efficacy and safety of endoscopic tattooing and to detect technical and clinical factors associated with its efficacy.
View Article and Find Full Text PDFBackground: Cardiovascular disease in obese individuals with type 2 diabetes is often associated with hyperleptinemia and leptin resistance, while other studies support that leptin has cardioprotective effects. Besides, the role of leptin in regulating cardiac atrophy or hypertrophy remains to be clearly defined. In fact, in rats with normal leptin sensitivity, the molecular underpinnings of the effects of central leptin regulating cardiac structural pathways remain poorly understood.
View Article and Find Full Text PDFObtention of customized dosage forms is one of the main attractions of 3D printing in pharmaceuticals. In this sense, children are one of the groups within the population with a greater need for drug doses adapted to their requirements (age, weight, pathological state…), but most 3D printed oral dosages are solid forms and, therefore, not suitable for them. This work developed patient-tailored medicinal gummies, an alternative oral dosage form with eye-catching appearance and appropriate organoleptic characteristics.
View Article and Find Full Text PDFThe correct administered activity of 18F-FCH is 0.1-0.14 mCi/Kg, which is equivalent to 3.
View Article and Find Full Text PDFObjective: To compare detectability of hyperfunctioning parathyroid tissue (HPT) by digital and analog 18F-fluorocholine PET/CT in patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT.
Materials And Methods: Thirty-three patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT were prospectively included. All patients accepted to be scanned by digital and analog PET/CT in the same imaging session after a single injection of 18F-fluorocholine.
Background: Fractional flow reserve (FFR) is a proven technology for guiding percutaneous coronary intervention, but it is not reimbursed despite the fact that it frequently allows to defer revascularization. Our goal was to determine the economic benefit of FFR on intermediate lesions, as well as the clinical endpoints at 1 year follow up.
Methods: Observational prospective study that included consecutive patients with intermediate lesions evaluated with FFR between April 2013 and March 2016.
Ageing is a major risk factor for the development of metabolic disorders linked to dyslipidemia, usually accompanied by increased adiposity. The goal of this work was to investigate whether avoiding an excessive increase in adiposity with ageing, via moderate chronic food restriction (FR), ameliorates postprandial dyslipidemia in a rat model of metabolic syndrome associated with ageing. Accordingly, we performed an oral lipid loading test (OLLT) in mature middle-aged (7 months) and middle-old-aged (24 months) Wistar rats fed ad libitum (AL) or under moderate FR for 3 months.
View Article and Find Full Text PDFCardiac fibromas are the second most common primary cardiac tumors in childhood. They only rarely present in adults. They are mainly located in the free wall of the ventricles and attached to the interventricular septum.
View Article and Find Full Text PDFHuman myogenic precursor cells have been isolated and expanded from a number of skeletal muscles, but alternative donor biopsy sites must be sought after in diseases where muscle damage is widespread. Biopsy sites must be relatively accessible, and the biopsied muscle dispensable. Here, we aimed to histologically characterize the cremaster muscle with regard number of satellite cells and regenerative fibres, and to isolate and characterize human cremaster muscle-derived stem/precursor cells in adult male donors with the objective of characterizing this muscle as a novel source of myogenic precursor cells.
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