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Advanced glycation end products (AGEs) disturb endothelial barrier function and contribute to age-related diseases. As microRNAs (miRNAs) are potential therapeutic agents, targeting AGEs-associated signaling using miRNAs in endothelial cells may be an effective intervention strategy for age-related vascular disorders. This study investigated the effects of AGEs on the endothelial cell senescence and barrier function in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with AGEs and transfected with miRNA-1-3p mimics to induce overexpression of miR-1-3p. Senescence-associated β-galactosidase (SA-β-Gal) staining and senescence-related proteins P53, P21, and P16 were detected to evaluate the endothelial cell senescence. The expression levels of myosin light chain kinase (MLCK) signaling and transendothelial electric resistance (TEER) were used to indicate endothelial barrier function. see more AGEs significantly increased SA-β-gal staining-positive cells accompanied by the upregulation of P53, P21, and P16 expression. AGEs also damaged endothelial barrier function by decreasing TEER and increasing zonula occludens protein 1, p-MLC/MLC, and MLCK. miRNA-1-3p was significantly reduced in HUVECs treated with AGEs. miR-1-3p overexpression decreased MLCK signal and improved AGEs-induced endothelial barrier function impairment. Meanwhile, miR-1-3p overexpression ameliorated oxidative stress and endothelial cell senescence induced by AGEs. AGEs induced endothelial cell senescence and endothelial barrier dysfunction by regulating miR-1-3p/MLCK signaling pathway.

 Hypoglycemia (HG) causes symptoms that can be fatal, and confers risk of dementia. Wearable devices can improve measurement and feedback to patients and clinicians about HG events and risk.

 The aim of the study is to determine whether vulnerable older adults could use wearables, and explore HG frequency over 2 weeks.

 First, 10 participants with diabetes mellitus piloted a continuous glucometer, physical activity monitor, electronic medication bottles, and smartphones facilitating prompts about medications, behaviors, and symptoms. They reviewed graphs of glucose values, and were asked about the monitoring experience. Next, a larger sample (

 = 70) wore glucometers and activity monitors, and used the smartphone and bottles, for 2 weeks. Participants provided feedback about the devices. Descriptive statistics summarized demographics, baseline experiences, behaviors, and HG.

 In the initial pilot, 10 patients aged 50 to 85 participated. Problems addressed included failure of the glucometer adhesive. s experienced HG, often serious in magnitude. This suggests important opportunities to improve wearability and decrease HG frequency among this population.

 Social media platforms have emerged as a valuable data source for public health research and surveillance. Monitoring of social media and user-generated data on the Web enables timely and inexpensive collection of information, overcoming time lag and cost of traditional health reporting systems.

 This article identifies personally experienced coronavirus disease 2019 (COVID-19) vaccine reactions expressed on Twitter and validate the findings against an established vaccine reactions reporting system.

 We collected around 3 million tweets from 1.4 million users between February 1, 2021, to January 31, 2022, using COVID-19 vaccines and vaccine reactions keyword lists. We performed topic modeling on a sample of the data and applied a modified F1 scoring technique to identify a topic that best differentiated vaccine-related personal health mentions. We then manually annotated 4,000 of the records from this topic, which were used to train a transformer-based classifier to identify likely personally experiencaluable supplementary data source for detecting vaccine adverse event mentions. Monitoring of online observations about new vaccine-related personal health experiences has the capacity to provide early warnings about emerging vaccine safety issues.

An effective clinical decision support system (CDSS) may address the current provider training barrier to offering preexposure prophylaxis (PrEP) to youth at risk for human immunodeficiency virus (HIV) infection. This study evaluated change in provider knowledge and the likelihood to initiate PrEP after exposure to a PrEP CDSS. A secondary objective explored perceived provider utility of the CDSS and suggestions for improving CDSS effectiveness.

This was a prospective study using survey responses from a convenience sample of pediatric providers who launched the interruptive PrEP CDSS when ordering an HIV test. McNemar's test evaluated change in provider PrEP knowledge and likelihood to initiate PrEP. Qualitative responses on CDSS utility and suggested improvements were analyzed using framework analysis and were connected to quantitative analysis elements using the merge approach.

Of the 73 invited providers, 43 had available outcome data and were included in the analysis. Prior to using the CDSS, 86% ofccess and uptake.

Our findings suggest that an interruptive PrEP CDSS attached to HIV test orders can be an effective tool to increase knowledge and likelihood to initiate PrEP among pediatric providers. Continual improvement of the PrEP CDSS based on provider feedback is required to optimize usability, effectiveness, and adoption. A highly usable PrEP CDSS may be a powerful tool to close the gap in youth PrEP access and uptake.

This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.

A systematic search for relevant studies was performed in 3 databases. Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included adiponectin, apelin, brain-derived neurotrophic factor, fetuin-A, fibroblast growth factor-21, follistatin, ghrelin, interleukin (IL)-6, IL-8, IL-10, IL-15, IL-18, leptin, myostatin, omentin, resistin, retinol-binding protein 4, tumor necrosis factor-α, and visfatin.

Forty randomized controlled trials were selected for data extraction (n = 2160). Exercise training induces changes in adiponectin, fetuin-A, fibroblast growth factor-21, IL-6, IL-10, leptin, resistin, and tumor necrosis factor-α levels but has no significant effects on apelin, IL-18, and ghrelin compared to controls. Physical exercise training favored large and positive changes in potes mellitus.RNA interference (RNAi) is a powerful innate immune mechanism to knock down translation of specific proteins whose machinery is conserved from plants to mammals. The template used to determine which mRNA's translation is inhibited is dsRNA, whose origin can range from viruses (long dsRNA, ∼100-1000s bp) to host (micro(mi)RNA, ∼20mers). While miRNA-mediated RNAi is well described in vertebrates, the ability of long dsRNA to guide RNAi-mediated translation inhibition in vertebrates is controversial. Indeed, as long dsRNA is so effective at inducing type I interferons (IFNs), and IFNs down-regulate RNAi machinery, it is believed that IFN-competent cells are not capable of using long dsRNA for RNAi. In the present study the ability of long, sequence specific dsRNA to knock down both host protein expression and viral replication is investigated in IFN-competent rainbow trout cells. Before exploring RNAi effects, the optimal dsRNA concentration that would funnel into RNAi without triggering the IFN response was detes, and while dsRNA-VHSV-N knocked down VHSV-IVa, dsRNA-VHSV-G and dsRNA-VHSV-M did not. This is the first study in fish to provide evidence that sequence specific long dsRNA induces potent gene expression silencing and antiviral responses in vitro via an RNAi-like mechanism instead of an IFN-dependent response.Tilapia lake virus (TiLV), an enveloped negative-sense single-stranded RNA virus, causes tilapia lake virus disease (TiLVD), which is associated with mass mortality and severe economic impacts in wild and farmed tilapia industries worldwide. In this study, we developed a chitosan nanoparticle TiLV immersion vaccine and assessed the efficacy of the vaccine in laboratory and field trials. Transmission electron microscopy showed that the inactivated vaccine had a particle size of 210.3 nm, while the nano inactivated vaccine had a spherical shape with a diameter of 120.4 nm. Further analysis using fluorescent staining and immunohistochemistry analysis revealed the mucoadhesive properties of the nanovaccine (CN-KV) through fish gills. We assessed the efficacy of an immersion-based TiLV nanovaccine using a cohabitation challenge model. The fish that received the nanovaccine showed better relative percent survival (RPS) at 68.17% compared with the RPS of the inactivated virus vaccine (KV) group at 25.01%. The CN-KV group also showed a higher TiLV-specific antibody response than the control and KV groups (p less then 0.05). Importantly, under field conditions, the fish receiving the CN-KV nanovaccine had better RPS at 52.2% than the nonvaccinated control group. Taken together, the CN-KV nanovaccinated fish showed better survival and antibody response than the control and KV groups both under laboratory control challenge conditions and field trials. The newly developed immersion-based nanovaccine is easy to administer in small fish, is less labor-intensive, and allows for mass vaccination to protect fish from TiLV infection.

Left ventricular (LV) remodelling (REM) ensuing after ST-elevation myocardial infarction (STEMI), has typically been studied by echocardiography, which has limitations, or cardiac magnetic resonance (CMR) in early phase that may overestimate infarct size (IS) due to tissue edema and stunning. This prospective, multicenter study investigated LV-REM performing CMR in the subacute phase, and 6months after STEMI.

patients with first STEMI undergoing successful primary angioplasty were consecutively enrolled. CMR was done at 30-days and 6-months. Primary endpoint was prevalence at 6months of LV-REM [≥12% increase in LV end-diastolic volume index (LV-REM

)]; LV-REM by end-systolic volume index increase ≥12% (LV-REM

) was also calculated. Of 325 patients enrolled, 193 with a full set of research-quality CMR images were analyzed. LV-REM

and LV-REM

were present in 36/193 (19%) and 34/193 (18%) patients, respectively. At follow up, LV ejection fraction (EF) improved in patients with or without LV-REM

, whils, driven by IS.

Limited data exist on the association between serum Klotho concentration and heart failure (HF).

We conducted a cross-sectional study of 13,625 participants aged 40-79years in the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Multivariable logistic regression models were used to examine the association between serum Klotho concentration (ln transformation) and HF. A total of 533 (2.9%) participants were identified to have HF, and participants with the lowest tertiles of serum Klotho concentration had the highest percentage of HF (T1 3.8% vs. T2 2.8% and T3 2.1%, P<0.001). After adjusting for potential confounders, ln (Klotho) was negatively and independently associated with the risk of HF (OR=0.55, 95% CI 0.36-0.84). Meanwhile, compared with the T1 group, a higher serum Klotho concentration was associated with a lower risk of HF (tertile 2 OR=0.93, 95% CI 0.69-1.29, tertile 3 OR=0.75, 95% CI 0.52-1.09, P for trend 0.022). Finally, subgroup analyses indicated that lower Klotho concentrations significantly correlated with an increased risk of HF in half of the subgroups.

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