Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells

Inflammation is associated with oxidative stress and characterized by elevated levels of damage-associated molecular pattern (DAMP) molecules released from injured or even living cells into the surrounding microenvironment. One of these endogenous danger signals is the extracellular mitochondrial DNA (mtDNA) containing evolutionary conserved unmethylated CpG repeats. Increased levels of reactive oxygen species (ROS) generated by recruited inflammatory cells modify mtDNA oxidatively resulting primarily in accumulation of 8-oxo-7,8-dihydroguanine (8-oxoG) lesions. In this study, we examined the impact of native and oxidatively modified mtDNAs on the phenotypic and functional properties of plasmacytoid dendritic cells (pDCs), which possess a fundamental role in the regulation of inflammation and T cell immunity. Treatment of human primary pDCs with native mtDNA up-regulated the expression of a co-stimulatory molecule (CD86), a specific maturation marker (CD83), and a main antigen-presenting molecule (HLA-DQ) on the cell surface, as well as increased TNF-α and IL-8 production from the cells. These effects were more apparent when pDCs were exposed to oxidatively modified mtDNA. Neither native nor oxidized mtDNA molecules were able to induce interferon (IFN)-α secretion from pDCs unless they formed a complex with human cathelicidin LL-37, an antimicrobial peptide. Interestingly, simultaneous administration of a Toll-like receptor (TLR)9 antagonist abrogated the effects of both native and oxidized mtDNAs on human pDCs. In a murine model, oxidized mtDNA also proved a more potent activator of pDCs compared to the native form, except for induction of IFN-α production. Collectively, we demonstrate here for the first time that elevated levels of 8-oxoG bases in the extracellular mtDNA induced by oxidative stress increase the immunostimulatory capacity of mtDNA on pDCs

DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells

BACKGROUND: The advent of Systems Biology has been accompanied by the blooming of pathway databases. Currently pathways are defined generically with respect to the organ or cell type where a reaction takes place. The cell type specificity of the reactions is the foundation of immunological research, and capturing this specificity is of paramount importance when using pathway-based analyses to decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and versatile resource for the interpretation of high-throughput data generated perturbing the signaling network of dendritic cells (DCs). RESULTS: Pathways are annotated using a novel data model, the Biological Connection Markup Language (BCML), a SBGN-compliant data format developed to store the large amount of information collected. The application of DC-ATLAS to pathway-based analysis of the transcriptional program of DCs stimulated with agonists of the toll-like receptor family allows an integrated description of the flow of information from the cellular sensors to the functional outcome, capturing the temporal series of activation events by grouping sets of reactions that occur at different time points in well-defined functional modules. CONCLUSIONS: The initiative significantly improves our understanding of DC biology and regulatory networks. Developing a systems biology approach for immune system holds the promise of translating knowledge on the immune system into more successful immunotherapy strategies

State of the art paper Augmented reality in neurosurgery

A b s t r a c t Neurosurgery is a medical specialty that relies heavily on imaging. The use of computed tomography and magnetic resonance images during preoperative planning and intraoperative surgical navigation is vital to the success of the surgery and positive patient outcome. Augmented reality application in neurosurgery has the potential to revolutionize and change the way neurosurgeons plan and perform surgical procedures in the future. Augmented reality technology is currently commercially available for neurosurgery for simulation and training. However, the use of augmented reality in the clinical setting is still in its infancy. Researchers are now testing augmented reality system prototypes to determine and address the barriers and limitations of the technology before it can be widely accepted and used in the clinical setting

An Integrated Variable-Magnitude Approach for Accessibility Evaluation of Healthcare Institute Web Pages

The World Wide Web has become an important platform for sharing a wide array of information within the world community. In the post-COVID-19 scenario, the web become a primary source of information in the context of healthcare information dissemination. Healthcare institutions, such as hospitals and clinics, utilize this platform to provide services to reach their target users. It is essential to evaluate the web pages of healthcare institutions and compute their accessibility score for people with disabilities or special needs. This paper presents a variable-magnitude approach to compute the accessibility score of healthcare web pages, considering several requirements of people with disabilities. To compute the accessibility score through the proposed approach, we considered two different components and integrated them to compute the accessibility score through the proposed algorithm. The proposed approach was experimentally applied to sixteen healthcare institutes’ web pages in Hungary. Based on the experiment’s results and the received feedback from an accessibility specialist, a set of suggestions is provided to minimize the accessibility barrier and improve the accessibility score for people with disabilities to access web resources without difficulty. The main contribution of this work is in enhancing awareness of web platform accessibility for web practitioners to improve accessibility, so that people with disabilities can effectively access web resources

Making Shopping Easy for People with Visual Impairment Using Mobile Assistive Technologies

People with visual impairment face various difficulties in their daily activities in comparison to people without visual impairment. Much research has been done to find smart solutions using mobile devices to help people with visual impairment perform tasks like shopping. One of the most challenging tasks for researchers is to create a solution that offers a good quality of life for people with visual impairment. It is also essential to develop solutions that encourage people with visual impairment to participate in social life. This study provides an overview of the various technologies that have been developed in recent years to assist people with visual impairment in shopping tasks. It gives an introduction to the latest direction in this area, which will help developers to incorporate such solutions into their research

Signaling Lymphocyte Activation Molecule Family 5 Enhances Autophagy and Fine-Tunes Cytokine Response in Monocyte-Derived Dendritic Cells via Stabilization of Interferon Regulatory Factor 8

Signaling lymphocyte activation molecule family (SLAMF) receptors are essential regulators of innate and adaptive immune responses. The function of SLAMF5/CD84, a family member with almost ubiquitous expression within the hematopoietic lineage is poorly defined. In this article, we provide evidence that in human monocyte-derived dendritic cells (moDCs) SLAMF5 increases autophagy, a degradative pathway, which is highly active in dendritic cells (DCs) and plays a critical role in orchestration of the immune response. While investigating the underlying mechanism, we found that SLAMF5 inhibited proteolytic degradation of interferon regulatory factor 8 (IRF8) a master regulator of the autophagy process by a mechanism dependent on the E3-ubiquitin ligase tripartite motif-containing protein 21 (TRIM21). Furthermore, we demonstrate that SLAMF5 influences the ratio of CD1a+ cells in differentiating DCs and partakes in the regulation of IL-1β, IL-23, and IL-12 production in LPS/IFNγ-activated moDCs in a manner that is consistent with its effect on IRF8 stability. In summary, our experiments identified SLAMF5 as a novel cell surface receptor modulator of autophagy and revealed an unexpected link between the SLAMF and IRF8 signaling pathways, both implicated in multiple human pathologies

Creation and Evaluation of a Preoperative Education Website for Hip and Knee Replacement Patients—A Pilot Study

Background and Objectives: There is limited research on the question of whether web-based preoperative education can improve surgical patient outcomes. The purpose of this pilot study was to determine the usability, utility, and feasibility of a website created to increase engagement and improve the quality of the preoperative education that patients having hip and knee arthroplasty surgery receive. Materials and Methods: A website was created, and its appearance was designed with evidence-based “menu-driven” drop-downs to make the screen options age-appropriate to the patient population; the content was supported with video and PDFs of educational material, the same or similar to the usual education provided to patients. The patient-specific outcomes included qualitative data regarding patient knowledge, satisfaction, utilities, and usability. These objectives were assessed based on the perceived health website usability questionnaire online survey. Eighty patients who met inclusion criteria were recruited, ranging in age from 40 to 65 years old. Among them, 52.5% were female, 71.25% were scheduled for knee arthroplasty, and 28.75% hip arthroplasty. The patients were randomly assigned to the paper only or website education cohorts in a 50:50 ratio. However, only 19 from each cohort participated in the survey questionnaire. Results and Conclusions: We hypothesized that findings would show that patients receiving web-based education would feel more knowledgeable about their procedure, have less anxiety, and greater satisfaction with the addition of the website content; and that nurses would report that a website could conserve nursing time and resources. The study revealed no statistically significant differences between the cohorts, with an Alpha level set at 0.05. However, survey results showed that patients using the website rated self-perceived increase in knowledge, and their satisfaction in the time to find and review the information was higher than that of the paper-only cohort. The nursing survey revealed that website education improved workflow, efficiency, and patient education