Reactive oxygen species rapidly increase endothelial ICAM-1 ability to bind neutrophils without detectable upregulation

We compared the effects of phorbol 12-myristate 13-acetate (PMA) and thrombin with those of nonlytic concentrations of reactive oxygen species (ROS) generated by hypoxanthine (HX)-xanthine oxidase (XO) on the adhesion properties of human umbilical cord vein endothelial cells (HUVEC) to resting polymorphonuclear neutrophils (PMN). PMN adherence to HX-XO-treated HUVEC was increased approximately twofold to 2.5-fold relative to untreated HUVEC, both immediately and after 2 hours. It was not additive to that induced by PMA or thrombin stimulation of HUVEC. ROS-induced adherence was not due to platelet-activating factor (PAF) or P-selectin expression, as it was neither antagonized by BN52021 (PAF receptor antagonist) nor inhibited by anti-P-selectin monoclonal antibody (MoAb), contrary to the increased adhesion of PMA- and thrombin-stimulated HUVEC. PMN preincubated with mannose-6-P or N- acetylneuraminic acid (sialic acid), but not mannose or galactose-6-P, showed reduced adherence to ROS-treated HUVEC, suggesting that carbohydrate molecules were expressed on the latter and served as the ligand for the PMN L-selectin. Intercellular adhesion molecule (ICAM- 1), constitutively present on the surface of resting HUVEC, was involved in the PMN adherence to ROS-treated HUVEC, since this adherence was inhibited by anti-ICAM-1, anti-CD11a, anti-CD11b, and anti-CD18 MoAbs. A non-CD18, non-ICAM-1-dependent mechanism is also involved in this adherence, since effects of these MoAbs were not additive; moreover, combinations of anti-CD18 and anti-ICAM-1 MoAbs with mannose-6-P and sialic acid completely inhibited PMN adherence. The increased binding of PMN to HX-XO-exposed HUVEC observed here involved IC-AM-1, but was independent of its upregulation, and another non-ICAM-1-dependent mechanism, in which carbohydrates expressed on HUVEC recognize L-selectin on PMN.     

Reorganization of myofilament proteins and decreased cGMP-dependent protein kinase in the human uterus during pregnancy

Excessive or premature contractions of uterine smooth muscle may contribute to preterm labor. Contractile stimuli induce myosin and actin filament interactions through calcium-dependent myosin phosphorylation. The mechanisms that maintain myometrial quiescence until term are not well established, but may include control of calcium levels by nitric oxide and cGMP signaling and thin filament (caldesmon and calponin) regulation. Previously, we reported that myometrial tissues from pregnant rats are not responsive to cGMP due to decreases in cGMP-dependent protein kinase. Considering the well documented differences in the endocrinology of parturition among species, this study was conducted to test the hypothesis that the levels and subcellular distribution of caldesmon, calponin, and cGMP-dependent protein kinase are regulated with the hormonal milieu of human pregnancy. Whereas cGMP-dependent protein kinase was significantly reduced in the human uterus during pregnancy, caldesmon expression was significantly increased, and both caldesmon and calponin were redistributed to a readily extractable subcellular pool. These data suggest that cGMP-dependent protein kinase does not mediate gestational quiescence. Redistribution of thin filament-associated proteins, however, may alter uterine smooth muscle tone or the cytoskeletal framework of myocytes to maintain gestation despite the substantial distention that accompanies all intrauterine pregnancies.     

The Psychosocial Impacts of COVID-19 on a Sample of Australian Adults: Cross-sectional Survey and Sentiment Analysis

BackgroundThe COVID-19 pandemic has had enormous impacts on people’s lives, including disruptions to their normal ways of behaving, working, and interacting with others. Understanding and documenting these experiences is important to inform the ongoing response to COVID-19 and disaster preparedness efforts.ObjectiveThe aim of this study was to examine the psychosocial impacts of COVID-19 on a sample of Australian adults.MethodsThe data analyzed were derived from a larger cross-sectional survey of Australian adults that was administered during the month of May 2020. Participants (N=3483) were asked in which ways COVID-19 had most greatly impacted them; the responses produced a text data set containing 1 COVID-19 impact story for each participant, totaling 86,642 words. Participants also completed assessments of their sociodemographic characteristics (sex, age, financial stress), level of concern related to COVID-19, personality trait profile, and satisfaction with life. Impact stories were analyzed using sentiment analysis and compared against the Theoretical Domains Framework to determine the most frequently impacted life domains. Finally, a multinomial regression analysis, stratified by participant sex, was conducted to identify the associations of psychological and demographic socializations with sentiment toward COVID-19.ResultsIn total, 3483 participants completed the survey, the majority of whom were female (n=2793, 80.2%). Participants’ impact stories were most commonly categorized as neutral (1544/3483, 44.3%), followed by negative (1136/3483, 32.6%) and positive (802/3483, 23.1%). The most frequently impacted life domains included behavioral regulation, environmental context and resources, social influences, and emotions, suggesting that the COVID-19 pandemic was impacting these areas of participants’ lives the most. Finally, the regression results suggested that for women, lower satisfaction with life and higher financial stress were associated with increased likelihood of negative, rather than positive, sentiment (P<.001); however, the proportion of variance in the sentiment that was explained was very small (<5%).ConclusionsParticipant sentiment toward COVID-19 varied. High rates of neutral and negative sentiment were identified. Positive sentiment was identified but was not as common. Impacts to different areas of people’s lives were identified, with a major emphasis on behavioral regulation and related domains such as social influences, environmental context and resources, and emotions. Findings may inform the development of mental health and social support resources and interventions to help alleviate the psychosocial consequences of disaster response measures.