The role of cue salience in the development of time concepts: Duration comparisons in young children.

It has been claimed that in the course of developing time concepts, young children go through a stage in which they conceptualize duration as being dependent on endings of events rather than on beginnings and endings. This conceptual deficit was proposed to account for children's greater success in comparing durations that differ in their endings than durations that differ in their beginnings. The present study analyzes the possibility that this phenomenon may be attributed mainly to perceptual salience rather than to conceptual deficit. 360 children from nursery school, kindergarten, and 1st grade were asked to compare the burning times of 2 lights that started and/or ended simultaneously. The role of attention to beginning vs end points in duration judgment was investigated by manipulating beginning- vs end-point salience via systematic variations of sequence of the problems presented. Correct comparisons of duration problems were found to be a function of the relative salience of beginning vs end points. Results support the salience attention model rather than the conceptual deficit account of duration judgments of young children. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intramuscular Exposure to a Lethal Dose of Ricin Toxin Leads to Endothelial Glycocalyx Shedding and Microvascular Flow Abnormality in Mice and Swine

Ricin toxin isolated from the castor bean (Ricinus communis) is one of the most potent and lethal molecules known. While the pathophysiology and clinical consequences of ricin poisoning by the parenteral route, i.e., intramuscular penetration, have been described recently in various animal models, the preceding mechanism underlying the clinical manifestations of systemic ricin poisoning has not been completely defined. Here, we show that following intramuscular administration, ricin bound preferentially to the vasculature in both mice and swine, leading to coagulopathy and widespread hemorrhages. Increased levels of circulating VEGF and decreased expression of vascular VE-cadherin caused blood vessel impairment, thereby promoting hyperpermeability in various organs. Elevated levels of soluble heparan sulfate, hyaluronic acid and syndecan-1 were measured in blood samples following ricin intoxication, indicating that the vascular glycocalyx of both mice and swine underwent extensive damage. Finally, by using side-stream dark field intravital microscopy imaging, we determined that ricin poisoning leads to microvasculature malfunctioning, as manifested by aberrant blood flow and a significant decrease in the number of diffused microvessels. These findings, which suggest that glycocalyx shedding and microcirculation dysfunction play a major role in the pathology of systemic ricin poisoning, may serve for the formulation of specifically tailored therapies for treating parenteral ricin intoxication.     

Quality of informal care is multidimensional.

Purpose: To demonstrate that assessing quality of informal care involves more than merely determining whether care recipient needs for assistance with activities of daily living (ADLs) are routinely satisfied. We investigated the extent to which potentially harmful behavior (PHB), adequate care, and exemplary care (EC) are empirically distinct dimensions of quality of care. Design: 237 care recipients completed the quality of care measures, and their caregivers completed psychosocial measures of their own depression, life events, cognitive status, and perceptions of pre-illness relationship quality. Results: Although PHB was moderately related to EC, adequate care was not associated with PHB and was only slightly related to EC. Psychosocial variables were not related to adequate care but were differentially associated with PHB and EC, providing additional evidence for the distinction between these measures of quality of care. Conclusions: ADL assistance can be adequate in the presence of PHB and/or the absence of EC. Declines in EC may signal increases in PHB, independent of adequacy of care. These findings produce a brief, portable, and more comprehensive instrument for assessing quality of informal care. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stressor-Induced Increases in Circulating,but Not Colonic,Cytokines Are Related to Anxiety-like Behavior and Hippocampal Inflammation in a Murine Colitis Model

Stressor exposure increases colonic inflammation. Because inflammation leads to anxiety-like behavior, we tested whether stressor exposure in mice recovering from dextran-sulfate-sodium (DSS)-induced colitis enhances anxiety-like behavior. Mice received 2% DSS for five consecutive days prior to being exposed to a social-disruption (SDR) stressor (or being left undisturbed). After stressor exposure, their behavior was tested and colitis was assessed via histopathology and via inflammatory-cytokine measurement in the serum and colon. Cytokine and chemokine mRNA levels in the colon, mesenteric lymph nodes (MLNs), hippocampus, and amygdala were measured with RT-PCR. SDR increased anxiety-like behaviors, which correlated with serum and hippocampal IL-17A. The stressor also reduced IL-1β, CCL2, and iNOS in the colonic tissue, but increased iNOS, IFNγ, IL-17A, and TNFα in the MLNs. A network analysis indicated that reductions in colonic iNOS were related to elevated MLN iNOS and IFNγ. These inflammatory markers were related to serum and hippocampal IL-17A and associated with anxiety-like behavior. Our data suggest that iNOS may protect against extra-colonic inflammation, and when suppressed during stress it is associated with elevated MLN IFNγ, which may coordinate gut-to-brain inflammation. Our data point to hippocampal IL-17A as a key correlate of anxiety-like behavior.     

Endogenous Opioid Peptides and Alternatively Spliced Mu Opioid Receptor Seven Transmembrane Carboxyl-Terminal Variants

There exist three main types of endogenous opioid peptides, enkephalins, dynorphins and β-endorphin, all of which are derived from their precursors. These endogenous opioid peptides act through opioid receptors, including mu opioid receptor (MOR), delta opioid receptor (DOR) and kappa opioid receptor (KOR), and play important roles not only in analgesia, but also many other biological processes such as reward, stress response, feeding and emotion. The MOR gene, OPRM1, undergoes extensive alternative pre-mRNA splicing, generating multiple splice variants or isoforms. One type of these splice variants, the full-length 7 transmembrane (TM) Carboxyl (C)-terminal variants, has the same receptor structures but contains different intracellular C-terminal tails. The pharmacological functions of several endogenous opioid peptides through the mouse, rat and human OPRM1 7TM C-terminal variants have been considerably investigated together with various mu opioid ligands. The current review focuses on the studies of these endogenous opioid peptides and summarizes the results from early pharmacological studies, including receptor binding affinity and G protein activation, and recent studies of β-arrestin2 recruitment and biased signaling, aiming to provide new insights into the mechanisms and functions of endogenous opioid peptides, which are mediated through the OPRM1 7TM C-terminal splice variants.     

The product cycle revisited: Knowledge intensity and firm internationalization

Abstract and Key Results

A multi-layer model for the early detection of COVID-19

Current COVID-19 screening efforts mainly rely on reported symptoms and the potential exposure to infected individuals. Here, we developed a machine-learning model for COVID-19 detection that uses four layers of information: (i) sociodemographic characteristics of the individual, (ii) spatio-temporal patterns of the disease, (iii) medical condition and general health consumption of the individual and (iv) information reported by the individual during the testing episode. We evaluated our model on 140 682 members of Maccabi Health Services who were tested for COVID-19 at least once between February and October 2020. These individuals underwent, in total, 264 516 COVID-19 PCR tests, out of which 16 512 were positive. Our multi-layer model obtained an area under the curve (AUC) of 81.6% when evaluated over all the individuals in the dataset, and an AUC of 72.8% when only individuals who did not report any symptom were included. Furthermore, considering only information collected before the testing episode—i.e. before the individual had the chance to report on any symptom—our model could reach a considerably high AUC of 79.5%. Our ability to predict early on the outcomes of COVID-19 tests is pivotal for breaking transmission chains, and can be used for a more efficient testing policy.     

Evaluation of mercury toxicity as a predictor of mercury bioavailability

Many studies on bioavailability of toxic metals have made the assumption that observation of toxicity is evidence thatthe metal was taken into the cells (i.e., was "bioavailable"). A second assumption is that results at the high concentrations necessary for toxic effect are applicable to the lower concentrations more commonly found in the environment. These assumptions were specifically tested for mercury (Hg(II)) toxicity (at concentrations of 0.25-50 nM Hg) and uptake (at lower concentrations of 0.005-0.015 nM Hg) in the aquatic bacterium, V. anguillarum. Toxicity was measured as reduction in levels of constitutively expressed bioluminescence in V. anguillarum pRB27. Hg(II) uptake was measured using the Hg(II)-inducible mer-lux operon in V. anguillarum pRB28. In experiments where the predominant Hg species was changed from HgCl2 to Hg(OH)2 or Hg(NH3)2(2+), toxicity results accurately predicted that there would be no effect of the dominant species on Hg(II) uptake at lower HgT concentrations. However, toxicity tests with these same ligands failed to predict that there would be an effect on Hg(II) uptake when conditions were changed from aerobic to anaerobic. Toxicity tests also failed to predict the effect of 5 mM histidine additions on Hg(II) uptake, as histidine addition protected cells completely from Hg toxicity under both aerobic and anaerobic conditions, at concentrations up to 50 nM Hg, but did not prevent Hg(II) uptake. Uptake occurred at low HgT concentrations (0.01 nM) at the same rate when histidine was added under aerobic conditions and was substantially increased under anaerobic conditions. Thus, toxicity assays for Hg under a variety of conditions were not always a reliable predictor of the effects of those conditions on Hg(II) uptake into the cell.     

Spatial and temporal presence of a wastewater-derived micropollutant plume in Lake Geneva

This study discusses the occurrence and environmental risk associated with a micropollutant plume originating from the direct discharge of treated wastewater into the Vidy Bay of Lake Geneva, Switzerland. The temporal variations and spatial extent of the plume and its effect on the presence of 39 pharmaceuticals and other micropollutants in the Vidy Bay were assessed over a 10 month period. A pronounced plume was observed from April to October, leading to locally elevated (up to 70-fold) pharmaceutical concentrations compared to the surrounding water column. For three of the measured substances, these plume-associated concentrations were sufficiently high to pose an ecotoxicological risk. The plume depth followed the thermal lake stratification, which moved to lower depths over the course of the warm seasons. Pharmaceutical hotspots associated with the plume were detected as far as 1.5 km downstream of the effluent wastewater outfall, but concentrations typically decreased with increasing distance from the wastewater outfall as a result of dilution and photodegradation. From November to January, when uniform temperature prevailed throughout the water column, no micropollutant plumes were detected. In contrast to pharmaceuticals, most pesticides showed homogeneous concentrations throughout the Vidy Bay during the whole study period, indicating that the effluent wastewater was not their dominant source. A strong linear correlation between electrical conductivity and concentrations of wastewater-derived micropollutants was identified. This relation will allow future estimates of wastewater-derived micropollutant concentrations via simple conductivity measurements.