HIPERTENSÃO E TECNOLOGIA: USO DE SOLUÇÃO DIGITAL E SEU IMPACTO NO ENGAJAMENTO DE PACIENTES E DESFECHOS CLÍNICOS / HYPERTENSION AND TECHNOLOGY: USE OF DIGITAL SOLUTION AND ITS IMPACT ON PATIENT ENGAGEMENT AND CLINICAL OUTCOMES

A hipertensão arterial sistêmica, principal fator de risco para as doenças cardiovasculares, é considerada a maior causa de mortes prematuras ao redor do mundo. Pacientes com baixa adesão ao tratamento apresentam maior risco de complicações, hospitalizações e morte prematura, além de aumentar a carga nos sistemas de saúde, onerando as economias nacionais. No Brasil, grande parte dos pacientes ainda apresenta um controle ruim dos fatores de risco cardiovascular, não atingindo as recomendações das principais diretrizes nacionais e internacionais. Com o intuito de trazer soluções para a falta de adesão, a tecnologia se torna uma importante aliada no automonitoramento e regularidade de tratamento. Aplicativos de automonitoramento com programas de gamificação são tecnologias emergentes, e seus resultados têm encorajado sua adoção porque estimulam os pacientes a se comprometerem com mudanças comportamentais e de estilo de vida. Elfie é uma solução digital inovadora e gratuita, validada pela Sociedade Brasileira de Cardiologia, pela Sociedade Brasileira de Diabetes e pela Associação Nacional de Atenção ao Diabetes, que, além de permitir que os usuários monitorem a sua condição física, também possam aprendam sobre sua saúde e recebam suporte personalizado por meio de um smartphone ou tablet, além de manter um banco de dados eletrônico para posterior consulta do próprio paciente e dos prestadores de cuidado à saúde, como médicos e nutricionistas. Os profissionais de saúde devem ser encorajados a discutir a utilidade desse tipo de ferramenta com seus pacientes, oferecendo, assim, a oportunidade de melhores desfechos clínicos e, consequentemente, reduzindo hospitalizações, mortalidade e custos em saúde.

Systemic Arterial Hypertension, the main risk factor for cardiovascular disease, is considered the greatest cause of premature deaths worldwide. Patients with low adherence to treatment are more susceptible for complications, hospitalizations, and premature death. In addition, there is an increasing burden on health systems and national economies for cardiovascular disease purposes. In Brazil, a large number of patients still have poor control of the risk factors, not reaching the recommendations of national and international guidelines. In order to attend with solutions, technology becomes an important ally in self-monitoring and regularity of treatment. Self-monitoring apps with gamification programs are emerging technologies which the results have encouraged their adoption because they inspire patients to commit with behavioral and lifestyle changes. Elfie is a novel free digital solution, endorsed by the Brazilian Society of Cardiology, the Brazilian Society of Diabetes and the National Diabetes Care Association. It allows the users to monitor and learn about their health and to receive personalized support through a smartphone or tablet. It also has a database that can be later accessed by the patient or healthcare providers, such as physicians and nutritionists. Healthcare professionals should be encouraged to discuss the advantages of these tools with their patients to offer an opportunity for better clinical outcomes and, consequently reduce hospitalizations, mortality and healthcare costs

The Role of Digital Technology and New Strategies in Engagement and Adherence Among Patients With Cardiometabolic Disease

Abstract This article explores challenges and barriers to managing cardiometabolic conditions, highlighting strategies and technologies for improving patient adherence. Approaches such as simplifying prescriptions, patient empowerment, health education, setting short-term goals, understanding social context, self-monitoring, and gamification have been effective in promoting adherence. The use of health apps for chronic diseases has also been increasing, facilitating medication adherence and self-monitoring. Integrating these approaches into clinical practice can lead to consistent outcomes and reduce care-associated costs.

Dr. Mathilde Krim: A Scientist and Her Fellowship Legacy.

On January 15, 2018, the world lost Dr. Mathilde Krim, a woman who changed the life of every person who has ever worked in HIV research. Variously remembered as a humanitarian, a socialite, a philanthropist, and a political activist, Dr. Krim was first and foremost a scientist. We highlight her pioneering research in fetal sex determination, as well as her activism during the unfolding AIDS epidemic, which culminated in the cofounding of amfAR, the Foundation for AIDS Research. Finally, we provide an analysis of the award named in honor of her inspirational leadership, the Mathilde Krim Fellowships in Basic Biomedical Research, which aims to catapult the careers of exceptional, early-stage researchers in the HIV/AIDS field. We follow applicants through the two-tier application process and dissect what defines a successful applicant at each stage. Through the Krim Fellowships, we hope to ensure that a new generation of HIV scientists can realize amfAR's goal of ending the AIDS epidemic.

Curing HIV: Moving Forward Faster.

There is enormous enthusiasm in the scientific community for finding a cure for HIV. Although much remains to be discovered regarding the mechanisms of viral persistence and how it may be disrupted, some assumptions regarding the goals of a cure, applicability to target populations, and what is required of the assays we employ, may lead to missed opportunities and discoveries and hamper the discovery of a product that will safely cure tens of millions of HIV-infected people around the world. The field will benefit from an awareness and critical interrogation of assumptions that may be implicit in their scientific pursuits.

FcγRIIB prevents inflammatory type I IFN production from plasmacytoid dendritic cells during a viral memory response.

The type I IFN (IFN-α) response is crucial for viral clearance during primary viral infections. Plasmacytoid dendritic cells (pDCs) are important early responders during systemic viral infections and, in some cases, are the sole producers of IFN-α. However, their role in IFN-α production during memory responses is unclear. We found that IFN-α production is absent during a murine viral memory response, despite colocalization of virus and pDCs to the splenic marginal zone. The absence of IFN was dependent on circulating Ab and was reversed by the transgenic expression of the activating human FcγRIIA receptor on pDCs. Furthermore, FcγRIIB was required for Sendai virus immune complex uptake by splenic pDCs in vitro, and internalization via FcγRIIb prevented cargo from accessing TLR signaling endosomes. Thus, pDCs bind viral immune complexes via FcγRIIB and prevent IFN-α production in vivo during viral memory responses. This Ab-dependent IFN-α regulation may be an important mechanism by which the potentially deleterious effects of IFN-α are prevented during a secondary infection.

A comprehensive study on the activity and deactivation of immobilized Lecitase Ultra in esterifications of food waste streams to monoacylglycerols.

Lecitase Ultra was immobilized on Amberlites XAD2 and XAD4, through physical entrapping under conventional stirring or ultrasound irradiation, and characterized by standard techniques. The resulting immobilized biocatalysts were utilized in the valorization of an acidic food-derived residue from a palm oil refining process to produce monoacylglycerols from isopropylidene glycerol under batch and continuous flow conditions. Results indicated that the immobilized biocatalysts could moderately convert the food waste residue (max. conversion 50-60 %), exhibiting interesting stability under continuous flow conditions.

Avaliação fisiológica invasiva da doença arterial coronária: papel da reserva de fluxo fracionado / Invasive physiological assessment of coronary artery disease: role of fractional flow reserve

Embora a angiografia coronária seja considerado o método de escolha para diagnóstica para a doença arterial coronária, ela representa um "luminograma" da superfície interna das artérias coronárias e, nem sempre fornece informação adequada e completa acerca do significa funcional de estenoses epicárdicas...

Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling.

Toll-like receptor (TLR) 3 is an endosomal TLR that mediates immune responses against viral infections upon activation by its ligand double-stranded RNA, a replication intermediate of most viruses. TLR3 is expressed widely in the body and activates both the innate and adaptive immune systems. However, little is known about how TLR3 intracellular trafficking and maturation are regulated. Here we show that newly synthesized endogenous TLR3 is transported through the ER and Golgi apparatus to endosomes, where it is rapidly cleaved. TLR3 protein expression is up-regulated by its own ligand, leading to the accumulation of its cleaved form. In agreement with its proposed role as a transporter, UNC93B1 expression is required for TLR3 cleavage and signaling. Furthermore, TLR3 signaling and cleavage are sensitive to cathepsin inhibition. Cleavage occurs between aa 252 and 346, and results in a functional receptor that signals upon activation. A truncated form of TLR3 lacking the N-terminal 345 aa also signals from acidic compartments in response to ligand activation. Screening of the human cathepsin family by RNA interference identified cathepsins B and H as key mediators of TLR3 processing. Taken together, our data indicate that TLR3 proteolytic processing is essential for its function, and suggest a mechanism of tight control of TLR3 signaling and thus immunity.

Dominant expression of the inhibitory FcgammaRIIB prevents antigen presentation by murine plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) are key regulators of the innate immune response, yet their direct role as APCs in the adaptive immune response is unclear. We found that unlike conventional DCs, immune complex (IC) exposed murine pDCs neither up-regulated costimulatory molecules nor activated Ag-specific CD4(+) and CD8(+) T cells. The inability of murine pDCs to promote T cell activation was due to inefficient proteolytic processing of internalized ICs. This defect in the IC processing capacity of pDCs results from a lack of activating FcgammaR expression (FcgammaRI, III, IV) and the dominant expression of the inhibitory receptor FcgammaRIIB. Consistent with this idea, transgenic expression of the activating human FcgammaRIIA gene, not present in the mouse genome, recapitulated the human situation and rescued IC antigenic presentation capacity by murine pDCs. The selective expression of FcgammaRIIB by murine pDCs was not strain dependent and was maintained even following stimulation with TLR ligands and inflammatory cytokines. The unexpected difference between the mouse and human in the expression of activating/inhibitory FcgammaRs has implications for the role of pDCs in Ab-modulated autoimmunity and anti-viral immunity.

Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II.

Lymphocyte activation gene-3 (LAG-3) is a CD4-related transmembrane protein expressed by regulatory T cells that binds MHC II on APCs. It is shown in this study that during Treg:DC interactions, LAG-3 engagement with MHC class II inhibits DC activation. MHC II cross-linking by agonistic Abs induces an ITAM-mediated inhibitory signaling pathway, involving FcgammaRgamma and ERK-mediated recruitment of SHP-1 that suppresses dendritic cell maturation and immunostimulatory capacity. These data reveal a novel ITAM-mediated inhibitory signaling pathway in DCs triggered by MHC II engagement of LAG-3, providing a molecular mechanism in which regulatory T cells may suppress via modulating DC function.

Fc gamma receptor IIB on dendritic cells enforces peripheral tolerance by inhibiting effector T cell responses.

The uptake of immune complexes by FcRs on APCs augments humoral and cellular responses to exogenous Ag. In this study, CD11c+ dendritic cells are shown to be responsible in vivo for immune complex-triggered priming of T cells. We examine the consequence of Ab-mediated uptake of self Ag by dendritic cells in the rat insulin promoter-membrane OVA model and identify a role for the inhibitory FcgammaRIIB in the maintenance of peripheral CD8 T cell tolerance. Effector differentiation of diabetogenic OT-I CD8+ T cells is enhanced in rat insulin promoter-membrane OVA mice lacking FcgammaRIIB, resulting in a high incidence of diabetes. FcgammaRIIB-mediated inhibition of CD8 T cell priming results from suppression of both DC activation and cross-presentation through activating FcgammaRs. Further FcgammaRIIB on DCs inhibited the induction of OVA-specific Th1 effectors, limiting Th1-type differentiation and memory T cell accumulation. In these MHC II-restricted responses, the presence of FcgammaRIIB only modestly affected initial CD4 T cell proliferative responses, suggesting that FcgammaRIIB limited effector cell differentiation primarily by inhibiting DC activation. Thus, FcgammaRIIB can contribute to peripheral tolerance maintenance by inhibiting DC activation alone or by also limiting processing of exogenously acquired Ag.