Introduction: CD8 cytotoxic T lymphocytes (CTLs) are highly effective in defending against viral infections and tumours. They are activated through the recognition of peptide-MHC-I complex by the T-cell receptor (TCR) and co-stimulation. This cognate interaction promotes the organisation of intimate cell-cell connections that involve cytoskeleton rearrangement to enable effector function and clearance of the target cell.
View Article and Find Full Text PDFPsychotic symptoms can be highly debilitating for those experiencing them. Community members, including family and friends, can play a crucial role in providing support to a person during the early stages of psychosis, provided they have the necessary resources. Mental health first aid guidelines for psychosis have been developed for high-income countries and this study aimed to adapt those guidelines for Brazil.
View Article and Find Full Text PDFT cell activation through TCR stimulation leads to the formation of the immunological synapse (IS), a specialized adhesion organized between T lymphocytes and antigen presenting cells (APCs) in which a dynamic interaction among signaling molecules, the cytoskeleton and intracellular organelles achieves proper antigen-mediated stimulation and effector function. The kinetics of molecular reactions at the IS is essential to determine the quality of the response to the antigen stimulation. Herein, we describe methods based on biochemistry, flow cytometry and imaging in live and fixed cells to study the activation state and dynamics of regulatory molecules at the IS in the Jurkat T cell line CH7C17 and primary human and mouse CD4 T lymphocytes stimulated by antigen presented by Raji and HOM2 B cell lines and human and mouse dendritic cells.
View Article and Find Full Text PDFCell proteostasis includes gene transcription, protein translation, folding of de novo proteins, post-translational modifications, secretion, degradation and recycling. By profiling the proteome of extracellular vesicles (EVs) from T cells, we have found the chaperonin complex CCT, involved in the correct folding of particular proteins. By limiting CCT cell-content by siRNA, cells undergo altered lipid composition and metabolic rewiring towards a lipid-dependent metabolism, with increased activity of peroxisomes and mitochondria.
View Article and Find Full Text PDFCalciphylaxis is a potencially disorder in patients with hyperphosphatemic familial tumoral calcinosis (HFTC). Patients commonly present livedo racemosa and retiform purpura, which may progress to necrosis and very painful ulcers. Treatment with sodium thiosulfate provides good results; however, intralesional and intravenous treatment can be limited by its adverse effects.
View Article and Find Full Text PDFTubulin post-translational modifications (PTMs) constitute a source of diversity for microtubule (MT) functions, in addition to the different isotypes of α and β-tubulin acting as building blocks of MTs. Also, MT-associated proteins (MAPs) confer different characteristics to MTs. The combination of all these factors regulates the stability of these structures that act as rails to transport organelles within the cell, facilitating the association of motor complexes.
View Article and Find Full Text PDFBackground: The production of carbapenem-hydrolyzing β-lactamases is one of the most concerning resistance mechanisms since it eliminates the last therapeutic option against multidrug resistant microorganisms.
Aim: To determine the production of KPC and NDM-1 type carbapenemases, using phenotypic and genotypic methods, in isolated enterobacteria in a clinical laboratory in the city of Maracay, Venezuela.
Methods: The production of carbapenemases was determined by phenotypic (according to the Malbrán algorithm) and genotypic methods (amplification of the blaNDM-1 and blaKPC genes by PCR) in clinical isolates of Enterobacteriaceae during the period March-August 2018.
Many people with chronic whiplash-associated disorders (WAD) have also symptoms of posttraumatic stress disorder (PTSD), but this is rarely considered in usual predominantly exercise-based interventions. We aimed to investigate the effectiveness of combined trauma-focused cognitive behavioural therapy (TF-CBT) and exercise compared with supportive therapy (ST) and exercise for people with chronic WAD and PTSD. A randomised controlled multicentre trial with concealed allocation, assessor blinding, and blinded analysis was conducted.
View Article and Find Full Text PDFBackground: Whereas HIV-1 has spread globally, HIV-2 is mainly found in West Africa where dual HIV-1/HIV-2 coinfection is nowadays uncommon. Herein, we report the rate, main characteristics, and treatment outcomes of all dually infected patients living in Spain.
Methods: We identified retrospectively all persons coinfected with HIV-1 recorded at the Spanish HIV-2 registry.
Chronic hepatitis C virus (HCV) infection is one of the major causes of death worldwide due to infectious agents. The advent of direct-acting antivirals has dramatically improved the chance of HCV elimination, even for patients with decompensated cirrhosis. Along with HCV cure, benefits are recognized in terms of regression of liver fibrosis and risk of hepatocellular carcinoma.
View Article and Find Full Text PDFJ Antimicrob Chemother
May 2019
Background: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2.
Methods: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort.
Background: Treatment with direct-acting antivirals (DAA) eradicates hepatitis C virus (HCV) from most chronic carriers. Information on regression of liver fibrosis and the influence of HIV is scarce in cured patients.
Methods: All consecutive HCV-infected individuals treated with DAA at our institution were examined.
Expert Rev Clin Pharmacol
May 2018
Current antiretroviral therapy allows to achieve and sustain maximal suppression of HIV replication in most treated patients. As result, the life expectancy of HIV-infected persons has improved dramatically and is nowadays similar to that of the HIV-negative population. However, oral antiretrovirals have to be taken daily and indefinitely to avoid resumption of HIV replication and selection of drug resistance.
View Article and Find Full Text PDFAbnormalities of mucus viscosity play a critical role in the pathogenesis of several respiratory diseases, including cystic fibrosis. Currently, there are no approaches to assess the rheological properties of mucin granule matrices in live cells. This is the first example of the use of a molecular rotor, a BODIPY dye, to quantitatively visualize the viscosity of intragranular mucin matrices in a large population of individual granules in differentiated primary bronchial epithelial cells using fluorescence lifetime imaging microscopy.
View Article and Find Full Text PDFThe systemic circulation offers larger resistance to the blood flow than the pulmonary system. Consequently, the left ventricle (LV) must pump blood with more force than the right ventricle (RV). The question arises whether the stronger pumping action of the LV is due to a more efficient action of left ventricular myosin, or whether it is due to the morphological differences between ventricles.
View Article and Find Full Text PDFOral DAA have demonstrated high efficacy as treatment of hepatitis C. However, the presence of resistance-associated substitutions (RAS) at baseline has occasionally been associated with impaired treatment response. Herein, we examined the impact of baseline RAS at the HCV NS5A gene region on treatment response in a real-life setting.
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