Abstract
Cardiac output (CO) measurement is crucial for the guidance of therapeutic decisions in critically ill and high-risk surgical patients. Newly developed completely non-invasive CO ...technologies are commercially available; however, their accuracy and precision have not recently been evaluated in a meta-analysis. We conducted a systematic search using PubMed, Cochrane Library of Clinical Trials, Scopus, and Web of Science to review published data comparing CO measured by bolus thermodilution with commercially available non-invasive technologies including pulse wave transit time, non-invasive pulse contour analysis, thoracic electrical bioimpedance/bioreactance, and CO2 rebreathing. The non-invasive CO technology was considered acceptable if the pooled estimate of percentage error was <30%, as previously recommended. Using a random-effects model, sd, pooled mean bias, and mean percentage error were calculated. An I2 statistic was also used to evaluate the inter-study heterogeneity. A total of 37 studies (1543 patients) were included. Mean CO of both methods was 4.78 litres min−1. Bias was presented as the reference method minus the tested methods in 15 studies. Only six studies assessed the random error (repeatability) of the tested device. The overall random-effects pooled bias (limits of agreement) and the percentage error were −0,13 −2.38 , 2.12 litres min−1 and 47%, respectively. Inter-study sensitivity heterogeneity was high (I2=83%, P<0.001). With a wide percentage error, completely non-invasive CO devices are not interchangeable with bolus thermodilution. Additional studies are warranted to demonstrate their role in improving the quality of care.
Polyphenols are naturally occurring compounds in plants and they are the most abundant antioxidants in the human diet. Due to their considerable structural diversity, this largely influences their ...bioavailability. Since a large proportion of polyphenols remains unabsorbed along the gastrointestinal tract, they may accumulate in the large intestine, where most of them are extensively metabolized by the intestinal microbiota. The formation of bioactive polyphenol-derived metabolites may also benefit the health status of the subjects, although the mechanisms have not been delineated. This review aims to highlight the impact of polyphenols on gut health and the modes of action could be through modulation of intestinal barrier function, innate and adaptive immune response, signaling pathways, as well as the ability to modify gut microbiota composition. The review will conclude by presenting future perspective and challenges of polyphenols application in food products to be used for preventing or treating diseases.
Dendritic cells in cancer immunology Murphy, Theresa L; Murphy, Kenneth M
Cellular & molecular immunology,
01/2022, Letnik:
19, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The clinical success of immune checkpoint therapy (ICT) has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of immune regulation. Much of the ...current translational efforts are aimed at enhancing ICT by identifying therapeutic targets that synergize with CTLA4 or PD1/PD-L1 blockade and are solidly developed on the basis of currently accepted principles. Expanding these principles through continuous basic research may help broaden translational efforts. With this mindset, we focused this review on three threads of basic research directly relating to mechanisms underlying ICT. Specifically, this review covers three aspects of dendritic cell (DC) biology connected with antitumor immune responses but are not specifically oriented toward therapeutic use. First, we review recent advances in the development of the cDC1 subset of DCs, identifying important features distinguishing these cells from other types of DCs. Second, we review the antigen-processing pathway called cross-presentation, which was discovered in the mid-1970s and remains an enigma. This pathway serves an essential in vivo function unique to cDC1s and may be both a physiologic bottleneck and therapeutic target. Finally, we review the longstanding field of helper cells and the related area of DC licensing, in which CD4 T cells influence the strength or quality of CD8 T cell responses. Each topic is connected with ICT in some manner but is also a fundamental aspect of cell-mediated immunity directed toward intracellular pathogens.
Basic leucine zipper transcription factor ATF-like (BATF), BATF2 and BATF3 belong to the activator protein 1 (AP-1) family of transcription factors, which regulate numerous cellular processes. ...Initially, BATF family members were thought to function only as inhibitors of AP-1-driven transcription, but recent studies have uncovered that these factors have unique, non-redundant and positive transcriptional activities in dendritic cells, B cells and T cells. The question of how BATF and BATF3 - which lack a transcriptional activation domain, unlike the AP-1 factors FOS and JUN - can exert unique positive transcriptional specificity has now been answered by the discovery that BATF molecules interact with members of the interferon-regulatory factor (IRF) family. The capacity of the BATF leucine zipper regions to mediate dimerization with AP-1 factors and also to define cooperative interactions with heterologous factors explains both the positive transcriptional activity of BATF proteins and how they activate distinct sets of target genes compared with FOS.
The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and ...T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2, but not Th17, cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite (HDM) challenge without affecting cytotoxic T lymphocyte (CTL), Th1 cell, or Th17 cell responses to herpes simplex virus, Toxoplasma gondii, and Citrobacter rodentium infections. Further, Klf4 deletion reduced IRF4 expression in pre-cDCs and resulted in selective loss of IRF4-expressing cDCs subsets in several tissues. These results indicate that Klf4 guides a transcriptional program promoting IRF4-expressing cDCs heterogeneity.
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•Klf4 is required for the development of a subset of IRF4-expressing cDCs•Klf4 deletion results in reduced pre-cDCs•A specific Klf4-dependent subset can be identified in several tissues•Klf4fl/flItgax-cre mice have selectively impaired Th2 cell immunity
The IRF4-expressing cDCs subset is highly heterogeneous and has been implicated in priming Th17, as well as Th2 cell immunity. Murphy and colleagues dissect this heterogeneity showing a developmental requirement for Klf4 on specific subsets across several tissues. Moreover, Klf4 guides a transcriptional program necessary for Th2 cell immunity.
During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8
T cells by
dependent CD8α
/XCR1
classical dendritic cells (cDC1s). We designed a functional CRISPR ...screen for previously unknown regulators of cross-presentation, and identified the BEACH domain-containing protein WDFY4 as essential for cross-presentation of cell-associated antigens by cDC1s in mice. However, WDFY4 was not required for major histocompatibility complex class II presentation, nor for cross-presentation by monocyte-derived dendritic cells. In contrast to
mice,
mice displayed normal lymphoid and nonlymphoid cDC1 populations that produce interleukin-12 and protect against
infection. However, similar to
mice,
mice failed to prime virus-specific CD8
T cells in vivo or induce tumor rejection, revealing a critical role for cross-presentation in antiviral and antitumor immunity.
B and T lymphocyte associated (BTLA) is an Ig domain superfamily protein with cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. Its ligand, herpesvirus entry mediator (HVEM), is a tumor ...necrosis factor receptor superfamily member. The unique interaction between BTLA and HVEM allows for a system of bidirectional signaling that must be appropriately regulated to balance the outcome of the immune response. HVEM engagement of BTLA produces inhibitory signals through SH2 domain-containing protein tyrosine phosphatase 1 (Shp-1) and Shp-2 association, whereas BTLA engagement of HVEM produces proinflammatory signals via activation of NF-kappaB. The BTLA-HVEM interaction is intriguing and quite complex given that HVEM has four other ligands that also influence immune responses, the conventional TNF ligand LIGHT and lymphotoxin alpha, as well as herpes simplex virus glycoprotein D and the glycosylphosphatidylinositol-linked Ig domain protein CD160. BTLA-HVEM interactions have been shown to regulate responses in several pathogen and autoimmune settings, but our understanding of this complex system of interactions is certainly incomplete. Recent findings of spontaneous inflammation in BTLA-deficient mice may provide an important clue.
Hydrogels are water-swollen polymer networks that have found a range of applications from biological scaffolds to contact lenses. Historically, their design has consisted primarily of static systems ...and those that exhibit simple degradation. However, advances in polymer synthesis and processing have led to a new generation of dynamic systems that are capable of responding to artificial triggers and biological signals with spatial precision. These systems will open up new possibilities for the use of hydrogels as model biological structures and in tissue regeneration.
Abstract Objective Accelerometers are being increasingly used in studies of physical activity (PA) among older adults, however the use of these monitors requires some specialized knowledge and ...up-to-date information on technological innovations. The purpose of this review article is to provide researchers with a guide to some commonly-used accelerometers in order to better design and conduct PA research with older adults. Methods A literature search was conducted to obtain all available literature on commonly-used accelerometers in older adult samples with specific attention to articles discussing research design. Results The use of accelerometers in older adults requires a basic understanding of the type being used, rationale for their placement, and attention to calibration when needed. The updated technology in some monitors should make study conduct less difficult, however comparison studies of the newer versus the older generation models will be needed. Conclusions Careful considerations for design and conduct of accelerometer research as outlined in this review should help to enhance the quality and comparability of future research studies.
In wireless environments, transmission and reception costs dominate system power consumption, motivating research effort on new technologies capable of reducing the footprint of the radio, paving the ...way for the Internet of Things. The most important challenge is to reduce power consumption when receivers are idle, the so called idle-listening cost. One approach proposes switching off the main receiver, then introduces new wake-up circuitry capable of detecting an incoming transmission, optionally discriminating the packet destination using addressing, then switching on the main radio only when required. This wake-up receiver technology represents the ultimate frontier in low power radio communication. In this paper, we present a comprehensive literature review of the research progress in wake-up radio (WuR) hardware and relevant networking software. First, we present an overview of the WuR system architecture, including challenges to hardware design and a comparison of solutions presented throughout the last decade. Next, we present various medium access control and routing protocols as well as diverse ways to exploit WuRs, both as an extension of pre-existing systems and as a new concept to manage low-power networking.
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