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Major cardiovascular events (MACEs) are a cause of major mortality worldwide. The narrowing and blockage of coronary arteries with atherosclerotic plaques are diagnosed and treated with percutaneous coronary intervention (PCI). During this procedure, coronary angiography (CAG) remains the most widely used guidance modality for the evaluation of the affected blood vessel. The measurement of the blood vessel diameter is an important factor to consider in order to decide if stent colocation is suitable for the intervention. In this regard, a small blood vessel (<2.75 mm) is majorly left without stent colocation; however, small vessel coronary artery disease (SvCAD) is a significant risk factor for the recurrence of MACEs, maybe due to the lack of a standardized treatment related to the diameter of the affected blood vessel; therefore, a more precise measurement is needed. The use of CAG for the measurement of the blood vessel diameter has some important limitations that can be improved with the use of newer techniques such as intravascular ultrasound (IVUS), although at higher costs, which might explain its underuse. To address differences in blood vessel diameter measurements and identify specific cases where IVUS might be of additional benefit for the patient, we conducted a retrospective study in patients who underwent PCI for MACEs with affection for at least one small blood vessel. We compared the measurements of the affected small blood vessels' diameter obtained by CAG and IVUS to identify cases of reclassification of the affected blood vessel; additionally, we underwent a multivariate analysis to identify risk factors associated with blood vessel reclassification. We included information from 48 patients with a mean ± SD age of 69.1 ± 11.9 years; 70.8% were men and 29.2% were women. The mean diameter with CAG and IVUS was 2.1 mm (95% CI 1.9–2.2), and 2.8 (2.8–3.0), respectively. The estimated difference was of 0.8 mm (95% CI 0.7–0.9). We found a significant positive low correlation in diameter measurements of small blood vessels obtained with CAG and IVUS (r = 0.1242 p = 0.014). In total, 37 (77%) patients had a reclassification of the affected blood vessel with IVUS. In 21 cases, the affected blood vessel changed from a small to a medium size (2.75–3.00 mm), and in 15 cases, the affected vessel changed from a small to a large size (<3.00 mm). The Bland–Altman plot was used to evaluate agreement in measurements with CAG and IVUS. The change in blood vessel classification with IVUs was important for the decision of intervention and stent collocation. The only variable associated with reclassification of blood vessels after adjustment in a multivariate analysis was T2D (type 2 diabetes) (p = 0 0.035). Our findings corroborate that blood vessels might appear smaller with CAG, especially in patients with T2D; therefore, at least in these cases, the use of IVUS is recommended over CAG. [ABSTRACT FROM AUTHOR]

Cognitive reflection, or the ability to inhibit intuitive and incorrect responses in favour of correct responses, predicts performance on a variety of cognitive tasks. The present study examined interventions to improve cognitive reflection. In two experiments, college students (N = 491) were assigned to one of three conditions, completed two versions of a cognitive reflection test (CRT), and then completed transfer tasks. Between the two CRTs, some participants were provided with elaborative feedback, others were instructed to consider additional responses for their initial responses and the final group was a control. In both experiments, CRT performance increased between the first and second CRT in the feedback and instruction groups, but not in the control group. There was little evidence, however, for transfer to other tasks. These results suggest that cognitive reflection performance can be improved with brief interventions but that this improvement may not transfer to related tasks. [ABSTRACT FROM AUTHOR]

Understanding severity in RSV: Almost all young children become infected with respiratory syncytial virus (RSV), but only a small proportion progress to severe disease, and certain immune responses have been shown to be harmful. To better understand immune signatures associated with mild or severe disease, Heinonen et al. performed transcriptomic and flow cytometry analysis on samples from RSV-infected children under the age of two. Children had either severe (inpatients) or mild disease (outpatients). Severe disease samples showed reduced viral loads and type I interferon signatures, as well as the presence of HLA-DRlow monocytes. Overall, a robust innate immune response seemed indicative of a more favorable outcome. Respiratory syncytial virus (RSV) is associated with major morbidity in infants, although most cases result in mild disease. The pathogenesis of the disease is incompletely understood, especially the determining factors of disease severity. A better characterization of these factors may help with development of RSV vaccines and antivirals. Hence, identification of a "safe and protective" immunoprofile induced by natural RSV infection could be used as a as a surrogate of ideal vaccine-elicited responses in future clinical trials. In this study, we integrated blood transcriptional and cell immune profiling, RSV loads, and clinical data to identify factors associated with a mild disease phenotype in a cohort of 190 children <2 years of age. Children with mild disease (outpatients) showed higher RSV loads, greater induction of interferon (IFN) and plasma cell genes, and decreased expression of inflammation and neutrophil genes versus children with severe disease (inpatients). Additionally, only infants with severe disease had increased numbers of HLA-DRlow monocytes, not present in outpatients. Multivariable analyses confirmed that IFN overexpression was associated with decreased odds of hospitalization, whereas increased numbers of HLA-DRlow monocytes were associated with increased risk of hospitalization. These findings suggest that robust innate immune responses are associated with mild RSV infection in infants. [ABSTRACT FROM AUTHOR]

Background: Human cytomegalovirus (CMV) infection is associated with renal allograft dysfunction and loss, particularly in combination with acute rejection. Emerging literature suggests that non-HLA antibodies may contribute to antibody-mediated rejection, but pathogen-induced antibodies have not been investigated in this context. This study examines the presence of CMV-induced antibodies in murine CMV (MCMV)-infected renal allografts during acute rejection., Methods: Intragraft immunoglobulin G (IgG) and complement C3 immunostaining were compared among allogeneic MCMV D-/R-, D+/R-, and D+/R+ renal transplants. Intragraft antibody deposition was examined in B cell-deficient recipients treated with MCMV immune sera. Antibody binding and complement-dependent cytotoxicity (CDC) of D-/R- and D+/R+ sera against infected renal tubular epithelial cells (TECs) were measured in vitro. IgG immunostaining was performed in D+/R+ allografts and native kidneys and in D+/R- allografts treated with ganciclovir to inhibit viral replication., Results: D+/R- and D+/R+ transplants had more abundant IgG and C3 deposition compared with D-/R- recipients. Greater IgG deposition was associated with more severe allograft injury in B cell-deficient recipients treated with MCMV immune sera compared with nonimmune sera. D+/R+ sera induced greater CDC of infected TECs compared with D-/R- sera. Native kidneys had lower IgG deposition compared with allografts, despite similar organ viral loads. Ganciclovir-treated allografts had reduced IgG deposition compared with untreated allografts., Conclusions: In this murine model, complement-fixing antibodies can deposit into MCMV-infected renal allografts, are associated with allograft damage, and can induce CDC of MCMV-infected renal TECs. The allogeneic response and viral replication may also contribute to intragraft antibody deposition., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Human cytomegalovirus (HCMV) donor positive (D+) serostatus with acute rejection is associated with renal allograft loss, but the impact of recipient positive (R+) serostatus is unclear. In an allogeneic renal transplant model, antiviral natural killer (NK) and CD8+ T cell memory responses in murine CMV (MCMV) D+/R+ transplants were compared to D-/R- and D+/R- transplants, with recipient infection varied by MCMV dose and strain. D+/R- transplants had high primary antiviral cytolytic (interferon-γ+) and cytotoxic (granzyme B+) NK responses, whereas NK memory responses were lower in D+/R+ recipients receiving a high primary MCMV dose. Despite MCMV immunity, D+/R+ recipients receiving a low MCMV dose showed primary-like high cytolytic and cytotoxic NK responses. D+/R+ transplants infected with different D/R strains had low cytolytic NK responses but high cytotoxic NK responses. NK memory also induced a novel TNF-α+ NK response among high-dose virus recipients. MCMV+ transplants had greater Th17 responses than MCMV-uninfected transplants and Th17 inhibition ameliorated graft injury. All MCMV+ recipients had similar CD8+ T cell responses. In sum, NK and Th17 responses, but not CD8+ T cells, varied according to conditions of primary recipient infection. This variability could contribute to variable graft outcomes in HCMV D+/R+ renal transplantation., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The liver has long been described as immunosuppressive, although the mechanisms underlying this phenomenon are incompletely understood. Hepatic stellate cells (HSCs), a population of liver nonparenchymal cells, are potent producers of the regulatory T cell (Treg)-polarizing molecules TGF-β1 and all-trans retinoic acid, particularly during states of inflammation. HSCs are activated during hepatitis C virus infection and may therefore play a role in the enrichment of Tregs during infection. We hypothesized that Ag presentation in the context of HSC activation will induce naive T cells to differentiate into Foxp3(+) Tregs. To test this hypothesis, we investigated the molecular interactions between murine HSCs, dendritic cells, and naive CD4(+) T cells. We found that HSCs alone do not present Ag to naive CD4(+) T cells, but in the presence of dendritic cells and TGF-β1, preferentially induce functional Tregs. This Treg induction was associated with retinoid metabolism by HSCs and was dependent on all-trans retinoic acid. Thus, we conclude that HSCs preferentially generate Foxp3(+) Tregs and, therefore, may play a role in the tolerogenic nature of the liver.