Project description:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was identified in China in 2019 as the causative agent of COVID-19, and quickly spread throughout the world, causing over 7 million deaths, of which 2 million occurred prior to the introduction of the first vaccine. In the following discussion, while recognising that complement is just one of many players in COVID-19, we focus on the relationship between complement and COVID-19 disease, with limited digression into directly-related areas such as the relationship between complement, kinin release, and coagulation. Prior to the 2019 COVID-19 outbreak, an important role for complement in coronavirus diseases had been established. Subsequently, multiple investigations of patients with COVID-19 confirmed that complement dysregulation is likely to be a major driver of disease pathology, in some, if not all, patients. These data fuelled evaluation of many complement-directed therapeutic agents in small patient cohorts, with claims of significant beneficial effect. As yet, these early results have not been reflected in larger clinical trials, posing questions such as who to treat, appropriate time to treat, duration of treatment, and optimal target for treatment. While significant control of the pandemic has been achieved through a global scientific and medical effort to comprehend the etiology of the disease, through extensive SARS-CoV-2 testing and quarantine measures, through vaccine development, and through improved therapy, possibly aided by attenuation of the dominant strains, it is not yet over. In this review, we summarise complement-relevant literature, emphasise its main conclusions, and formulate a hypothesis for complement involvement in COVID-19. Based on this we make suggestions as to how any future outbreak might be better managed in order to minimise impact on patients.
Project description:Uncertainty monitoring is a core property of metacognition, allowing individuals to adapt their decision-making strategies depending on the state of their knowledge. Although it has been argued that other animals share these metacognitive abilities, only humans seem to possess the ability to explicitly communicate their own uncertainty to others. It remains unknown whether this capacity is present early in development, or whether it emerges later with the ability to verbally report one's own mental states. Here, using a nonverbal memory-monitoring paradigm, we show that 20-month-olds can monitor and report their own uncertainty. Infants had to remember the location of a hidden toy before pointing to indicate where they wanted to recover it. In an experimental group, infants were given the possibility to ask for help through nonverbal communication when they had forgotten the toy location. Compared with a control group in which infants had no other option but to decide by themselves, infants given the opportunity to ask for help used this option strategically to improve their performance. Asking for help was used selectively to avoid making errors and to decline difficult choices. These results demonstrate that infants are able to successfully monitor their own uncertainty and share this information with others to fulfill their goals.
Project description:Several studies suggest that "don't know" (DK) responses to risk perception items may represent meaningful expressions of uncertainty about disease risk. However, researchers are often discouraged from including a DK response option in survey items due to concerns about respondents overusing it to minimize cognitive effort-a phenomenon often referred to as satisficing. Our objective was to investigate whether patterns of DK responses to risk perception survey items were consistent with satisficing behavior. We conducted a secondary analysis of survey data from 814 parents and guardians (hereafter caregivers) of children with asthma. Caregivers answered 18 items assessing their perceived risk of their child experiencing two types of poor asthma outcomes: asthma exacerbation, and low asthma control. We examined differences in the frequency and distribution of DK responses across all 18 items and by type of risk perception item (i.e., 2 vs. 5 response options, absolute vs. comparative risk). We found that 32% (n=548) of respondents marked DK at least once. Of the 266 caregivers who provided any DK response, most did so for only 1 or 2 items (51.9%, n=138), and only 6% (n=15) answered DK to more than half of the items. Using random coefficient Poisson models, we found more DK responding for dichotomous absolute (30.1%) than ordinal absolute items (5.3%), b=1.72, p<.001. We also found fewer DK responses to the ordinal absolute items than the comparative items (8.2%), b=-0.49, p<.001. Using Chi-square tests, we found that inattentive responding was not associated with responding DK. Our findings suggest that satisficing is unlikely to completely explain DK responding to perceived risk survey items. Researchers who exclude DK response options from risk perception survey items may obtain an incomplete understanding of their study sample's beliefs about risk.
Project description:The proteins soluble ST2 (sST2) and galectin-3 are currently gaining mounting interest as candidate biomarkers in cardiac disease. Both, sST2 and galectin-3 have been included in the 2013 ACCF/AHA guideline for additive risk stratification of patients with acute and chronic heart failure. The aim of this review is to provide information on analytical considerations of measuring circulating sST2 and galectin-3 including knowledge on in vitro stability, biological variation and reference ranges of both analytes.
Project description:Within the last decade, research regarding the human gut microbiome has exploded. While the gastrointestinal tract was once regarded simply as a digestive organ, new technologies have led the science world to wonder about the impact that the gut microbiota may have on human health and disease. The gut microbiome is now becoming known for its role in metabolism, immune defense, and behavior. From in utero variations to those that rapidly occur post partum, our gut microbiome changes with age, environment, stress, diet, and health status as well as medication exposure. This article reviews what is currently known regarding various influences on the gut microbiome and is meant to encourage the reader to further explore the unknown.
Project description:Adult psychopaths have deficits in emotional processing and inhibitory control, engage in morally inappropriate behavior, and generally fail to distinguish moral from conventional violations. These observations, together with a dominant tradition in the discipline which sees emotional processes as causally necessary for moral judgment, have led to the conclusion that psychopaths lack an understanding of moral rights and wrongs. We test an alternative explanation: psychopaths have normal understanding of right and wrong, but abnormal regulation of morally appropriate behavior. We presented psychopaths with moral dilemmas, contrasting their judgments with age- and sex-matched (i) healthy subjects and (ii) non-psychopathic, delinquents. Subjects in each group judged cases of personal harms (i.e. requiring physical contact) as less permissible than impersonal harms, even though both types of harms led to utilitarian gains. Importantly, however, psychopaths' pattern of judgments on different dilemmas was the same as those of the other subjects. These results force a rejection of the strong hypothesis that emotional processes are causally necessary for judgments of moral dilemmas, suggesting instead that psychopaths understand the distinction between right and wrong, but do not care about such knowledge, or the consequences that ensue from their morally inappropriate behavior.
Project description:IgA nephropathy (IgAN), the most common primary glomerular disease worldwide, is characterized by glomerular deposition of IgA1-containing immune complexes. The IgA1 hinge region (HR) has up to six clustered O-glycans consisting of Ser/Thr-linked N-acetylgalactosamine usually with β1,3-linked galactose and variable sialylation. Circulating levels of IgA1 with abnormally O-glycosylated HR, termed galactose-deficient IgA1 (Gd-IgA1), are increased in patients with IgAN. Current evidence suggests that IgAN is induced by multiple sequential pathogenic steps, and production of aberrantly glycosylated IgA1 is considered the initial step. Thus, the mechanisms of biosynthesis of aberrantly glycosylated IgA1 and the involvement of aberrant glycoforms of IgA1 in disease development have been studied. Furthermore, Gd-IgA1 represents an attractive biomarker for IgAN, and its clinical significance is still being evaluated. To elucidate the pathogenesis of IgAN, it is important to deconvolute the biosynthetic origins of Gd-IgA1 and characterize the pathogenic IgA1 HR O-glycoform(s), including the glycan structures and their sites of attachment. These efforts will likely lead to development of new biomarkers. Here, we review the IgA1 HR O-glycosylation in general and the role of aberrantly glycosylated IgA1 in the pathogenesis of IgAN in particular.
Project description:Extracorporeal life support (ECLS) is increasingly used in the management of patients with severe cardiopulmonary disease. Infections are frequently the etiologies underlying the respiratory, and occasionally cardiac, failure that necessitates ECLS. Just as importantly, infections are among the most commonly reported adverse events during ECLS. Infections in this setting may be the sequelae of prolonged critical illness or of underlying immune dysregulation; they may be hospital-acquired infections, and they may or may not be attributable to the presence of ECLS itself, the latter being an aspect that can be difficult to determine. Current registry data and evidence from the literature offer some insights, but also leave open many questions regarding the nature and significance of infections reported both before and during ECLS, including the question of any causal link between ECLS and the development of infections. An ongoing lack of consistency in the identification, diagnosis, management, and prevention of infections during ECLS is limiting our ability to interpret literature data and thus highlighting the need for more rigorous investigation and standardization of definitions. This review aims to characterize the current understanding of infections associated with the use of ECLS, taking into account data from the updated Extracorporeal Life Support Organization Registry, which provides important context for understanding the epidemiology and outcomes of these patients.