The key outputs of this project will be the development of a digital infrastructure, including a backend distributed ledger system and an app-based user interface.

This infrastructure is expected to improve the accuracy and efficiency of adverse event reporting systems by enabling the monitoring of specific medicines or medical devices over their life course while protecting patients’ personal health data.

PRR1-10.2196/28616.

PRR1-10.2196/28616.

A strong association exists between consuming a healthy diet and lowering cholesterol levels among individuals with high cholesterol. However, implementing and sustaining a healthy diet in the real world is a major challenge. Digital technologies are at the forefront of changing dietary behavior on a massive scale, as they can reach broad populations. There is a lack of evidence that has examined the benefit of a digital nutrition intervention, especially one that incorporates nutrition education, meal planning, and food ordering, on cholesterol levels among individuals with dyslipidemia.

The aim of this observational longitudinal study was to examine the characteristics of people with dyslipidemia, determine how their status changed over time, and evaluate the changes in total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and triglycerides among individuals with elevated lipids who used Foodsmart, a digital nutrition platform that integia at baseline improved their lipid levels to normal by the end of follow-up. Using multivariate logistic regression, we found that baseline obesity (odds ratio [OR] 2.57, 95% CI 1.25-5.29; P=.01) and Nutriscore (OR 1.04, 95% CI 1.00-1.09; P=.04) were directly associated with achieving normal lipid levels. Participants with elevated lipid levels saw improvements as follows HDL-C increased by 38.5%, total cholesterol decreased by 6.8%, cholesterol ratio decreased by 20.9%, LDL-C decreased by 12.9%, non-HDL-C decreased by 7.8%, and triglycerides decreased by 10.8%.

This study characterized users of the Foodsmart platform who had dyslipidemia and found that users with elevated lipid levels showed improvements in the levels over time.

This study characterized users of the Foodsmart platform who had dyslipidemia and found that users with elevated lipid levels showed improvements in the levels over time.Optical coherence tomography (OCT) has been increasingly utilised to guide percutaneous coronary intervention (PCI). Despite the diagnostic utility of OCT, facilitated by its high resolution, the impact of intracoronary OCT on clinical practice has thus far been limited. Difficulty in transitioning from intravascular ultrasound (IVUS), complex image interpretation, lack of a standardised algorithm for PCI guidance, and paucity of data from prospective clinical trials have contributed to the modest adoption. Herein, we provide a comprehensive up-do-date overview on the utility of OCT in coronary artery disease, including technical details, device set-up, simplified OCT image interpretation, recognition of the imaging artefacts, and an algorithmic approach for using OCT in PCI guidance. We discuss the utility of OCT in acute coronary syndromes, provide a summary of the clinical trial data, list the work in progress, and discuss the future directions.

Hepatic platelet accumulation contributes to acetaminophen (APAP)-induced liver injury (AILI). However, little is known about the molecular pathways involved in platelet recruitment to the liver and whether targeting such pathways could attenuate AILI.

Mice were fasted overnight before intraperitoneally (

) injected with APAP at a dose of 210 mg/kg for male mice and 325 mg/kg for female mice. Platelets adherent to Kupffer cells were determined in both mice and patients overdosed with APAP. The impact of α-chitinase 3-like-1 (α-Chi3l1) on alleviation of AILI was determined in a therapeutic setting, and liver injury was analyzed.

The present study unveiled a critical role of Chi3l1 in hepatic platelet recruitment during AILI. Increased Chi3l1 and platelets in the liver were observed in patients and mice overdosed with APAP. Compared to wild-type (WT) mice,

mice developed attenuated AILI with markedly reduced hepatic platelet accumulation. Mechanistic studies revealed that Chi3l1 signaled through CD4ies). The contents do not represent the views of the US Department of Veterans Affairs or the US Government.The nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport, and its dysfunction has been associated with many diseases. The metazoan NPC subcomplex RanBP2, which consists of RanBP2 (Nup358), RanGAP1-SUMO1, and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in regulation of NPC remain poorly understood. Here, we show that in human and murine T cells, following T-cell receptor (TCR) stimulation, protein kinase C-θ (PKC-θ) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-θ to the NPC, where it interacts with and phosphorylates RanGAP1 on Ser504 and Ser506. click here RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-θ as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC subcomplex.Nuclear factor 90 (NF90) is a novel virus sensor that serves to initiate antiviral innate immunity by triggering stress granule (SG) formation. However, the regulation of the NF90-SG pathway remains largely unclear. We found that Tim-3, an immune checkpoint inhibitor, promotes the ubiquitination and degradation of NF90 and inhibits NF90-SG-mediated antiviral immunity. Vesicular stomatitis virus (VSV) infection induces the up-regulation and activation of Tim-3 in macrophages, which in turn recruit the E3 ubiquitin ligase TRIM47 to the zinc finger domain of NF90 and initiate a proteasome-dependent degradation via K48-linked ubiquitination at Lys297. Targeted inactivation of Tim-3 enhances the NF90 downstream SG formation by selectively increasing the phosphorylation of protein kinase R and eukaryotic translation initiation factor 2α, the expression of SG markers G3BP1 and TIA-1, and protecting mice from VSV challenge. These findings provide insights into the crosstalk between Tim-3 and other receptors in antiviral innate immunity and its related clinical significance.