Illumina Sequencing in Conjunction with Propidium Monoazide to Identify Live Bacteria After Antiseptic Treatment in a Complex Oral Biofilm: A Study Using an Ex Vivo Supragingival Biofilm Model.

: The evaluation of the efficacy of antibacterial treatments in complex oral ecosystems is limited by the inability to differentiate live from dead bacteria using omic techniques. The objective of this study was therefore to assess the ability of the combination of the 16S rRNA Illumina sequencing methodology and the action of propidium monoazide (PMA) to study viable bacterial profiles in oral biofilms after exposure to an antiseptic compound. : Cariogenic supragingival biofilms were developed in an ex vivo model for 96 h, using saliva from healthy volunteers.

Cysteamine dioxygenase (ADO) governs cancer cell mitochondrial redox homeostasis through proline metabolism.

2-Aminoethanethiol dioxygenase (ADO) is a thiol dioxygenase that sulfinylates cysteamine and amino-terminal cysteines in polypeptides. The pathophysiological roles of ADO remain largely unknown. Here, we demonstrate that ADO expression represents a vulnerability in cancer cells, as ADO depletion led to loss of proliferative capacity and survival in cancer cells and reduced xenograft growth.

Metabolomics and Biochemical Benefits of Multivitamin and Multimineral Supplementation in Healthy Individuals: A Pilot Study.

Scientific evidence regarding the effectiveness of vitamin and mineral supplements in healthy individuals remains scarce. In a randomized, double-blind study, 30 healthy individuals were assigned to receive a single daily dose of multivitamin and multimineral supplementation or a double daily dose for 30 days. Before and after the intake, an untargeted metabolomics assay for serum metabolites was conducted by hydrophilic interaction liquid chromatography-mass spectrometry, and clinical assessments of peripheral blood samples were performed.

Dabrafenib Alters MDSC Differentiation and Function by Activation of GCN2.

Unlabelled: The effect of targeted therapeutics on anticancer immune responses is poorly understood. The BRAF inhibitor dabrafenib has been reported to activate the integrated stress response (ISR) kinase GCN2, and the therapeutic effect has been partially attributed to GCN2 activation. Because ISR signaling is a key component of myeloid-derived suppressor cell (MDSC) development and function, we measured the effect of dabrafenib on MDSC differentiation and suppressive activity.

Pro-angiogenic changes of T-helper lymphocytes in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a rare inherited disease due to heterozygous loss-of-function mutations on the BMP9/10 pathway ( or mainly). HHT endothelial cells are prone to lose their quiescence, leading to progressive appearance of numerous telangiectases on skin and mucosa (complicated by epistaxis and anemia), and to larger arteriovenous malformations in lungs, liver and brain. HHT is also associated with T lymphocyte abnormalities, which are currently poorly understood.

Evidence of the Beneficial Impact of Three Probiotic-Based Food Supplements on the Composition and Metabolic Activity of the Intestinal Microbiota in Healthy Individuals: An Ex Vivo Study.

Scientific evidence has increasingly supported the beneficial effects of probiotic-based food supplements on human intestinal health. This ex vivo study investigated the effects on the composition and metabolic activity of the intestinal microbiota of three probiotic-based food supplements, containing, respectively, (1) ES1, (2) NCFM, and (3) a combination of NCFM, Lpc-37™, Bi-07™, and Bl-04™. This study employed fecal samples from six healthy donors, inoculated in a Colon-on-a-plate system.

Dabrafenib alters MDSC differentiation and function by activation of GCN2.

The effect of targeted therapeutics on anti-cancer immune responses is poorly understood. The BRAF inhibitor dabrafenib has been reported to activate the integrated stress response (ISR) kinase GCN2, and the therapeutic effect has been partially attributed to GCN2 activation. Since ISR signaling is a key component of myeloid-derived suppressor cell (MDSC) development and function, we measured the effect of dabrafenib on MDSC differentiation and suppressive activity.

Regulatory T-cell dysfunctions are associated with increase in tumor necrosis factor α in autoimmune hemolytic anemia and participate in Th17 polarization.

Warm autoimmune hemolytic anemia (wAIHA) is a rare acquired autoimmune disease mediated by antibodies targeting red blood cells. The involvement of CD4 T-helper cells has been scarcely explored, with most findings extrapolated from animal models. Here, we performed quantification of both effector T lymphocytes (Teff) and regulatory T cells (Treg), associated with functional and transcriptomic analyses of Treg in human wAIHA.

The transcription factor IRF2 drives interferon-mediated CD8 T cell exhaustion to restrict anti-tumor immunity.

Type I and II interferons (IFNs) stimulate pro-inflammatory programs that are critical for immune activation, but also induce immune-suppressive feedback circuits that impede control of cancer growth. Here, we sought to determine how these opposing programs are differentially induced. We demonstrated that the transcription factor interferon regulatory factor 2 (IRF2) was expressed by many immune cells in the tumor in response to sustained IFN signaling.

Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial.

Background: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation.

Methods: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC.

T-cell immune response predicts the risk of critical SARS-Cov2 infection in hospitalized COVID-19 patients.

Introduction: This study aimed to identify markers of disease worsening in patients hospitalized for SARS-Cov2 infection.

Patients And Methods: Patients hospitalized for severe recent-onset (<1 week) SARS-Cov2 infection were prospectively included. The percentage of T-cell subsets and plasma IL-6 at admission (before any steroid therapy) were compared between patients who progressed to a critical infection and those who did not.

Metataxonomic and metabolomic evidence of biofilm homeostasis disruption related to caries: An in vitro study.

The ecological dysbiosis of a biofilm includes not only bacterial changes but also changes in their metabolism. Related to oral biofilms, changes in metabolic activity are crucial endpoint, linked directly to the pathogenicity of oral diseases. Despite the advances in caries research, detailed microbial and metabolomic etiology is yet to be fully clarified.

Antithrombotic therapy and clinical outcomes at 1 year in the Spanish cohort of the EORP-AF Long-term General Registry.

Background: Atrial fibrillation (AF) increases the risk of thromboembolism. We investigate the efficacy and safety of oral anticoagulation (OAC) therapy and explored the number needed to treat for net effect (NNTnet) of OAC in the Spanish cohort of the EURObservational Research Programme-AF (EORP-AF) Long-term General Registry.

Methods: The EORP-AF General Registry is a prospective, multicentre registry conducted in ESC countries, including consecutive AF patients.

Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis.

Objectives: To study the percentage, suppressive function and plasticity of Treg in giant cell arteritis (GCA), and the effects of glucocorticoids and tocilizumab.

Methods: Blood samples were obtained from 40 controls and 43 GCA patients at baseline and after treatment with glucocorticoids + IV tocilizumab ( = 20) or glucocorticoids ( = 23). Treg percentage and phenotype were assessed by flow cytometry.

Executive-function tasks in patients with mild cognitive impairment and Alzheimer's Disease: Effects of decline and gender.

It is exceedingly rare to find studies that analyze the effect of gender differences in executive-function tasks in normal cognitive aging, Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). The objective of the present study was to analyze the mean differences in performance in four executive-function tasks, the Clock Drawing Test verbal-command, Clock Drawing Test-copy, Phonetic Fluency Test and Trail Making Test-A, according to the gender and impairment group variables. A total of 90 participants (30 patients with Alzheimer's Disease, 30 patients with Mild Cognitive Impairment, and 30 healthy elderly participants; 50% men and 50% women in each group) took part in the study.

Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments.

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to both a peripheral destruction of platelets and an inappropriate bone marrow production. Although the primary triggering factors of ITP remain unknown, a loss of immune tolerance-mostly represented by a regulatory T-cell defect-allows T follicular helper cells to stimulate autoreactive splenic B cells that differentiate into antiplatelet antibody-producing plasma cells. Glycoprotein IIb/IIIa is the main target of antiplatelet antibodies leading to platelet phagocytosis by splenic macrophages, through interactions with Fc gamma receptors (FcγRs) and complement receptors.

Mucosal-associated invariant T cells in Giant Cell Arteritis.

This study aimed to assess the implication of mucosal-associated invariant T (MAIT) cells in GCA. Blood samples were obtained from 34 GCA patients (before and after 3 months of treatment with glucocorticoids (GC) alone) and compared with 20 controls aged >50 years. MAIT cells, defined by a CD3CD4TCRγδTCRVα7.