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Background: Toxic metals, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg), may be associated with a higher risk of gestational hypertension and preeclampsia, whereas manganese (Mn) is an essential metal that may be protective. OBJECTIVES: We estimated the individual, independent, and joint associations of Pb, Cd, As, Hg, and Mn on the risk of developing gestational hypertension and preeclampsia in a cohort of Canadian women. Methods: Metal concentrations were analyzed in first and third trimester maternal blood (n = 1,560). We measured blood pressure after 20 wk gestation to diagnose gestational hypertension, whereas proteinuria and other complications defined preeclampsia. We estimated individual and independent (adjusted for coexposure) relative risks (RRs) for each doubling of metal concentrations and examined interactions between toxic metals and Mn. We used quantile g-computation to estimate the joint effect of trimester-specific exposures. Results: Each doubling of third trimester Pb (RR = 1.54; 95% CI: 1.06, 2.22) and first trimester blood As (RR = 1.25; 95% CI: 1.01, 1.58) was independently associated with a higher risk of developing preeclampsia. First trimester blood As (RR = 3.40; 95% CI: 1.40, 8.28) and Mn (RR = 0.63; 95% CI: 0.42, 0.94) concentrations were associated with a higher and lower risk, respectively, of developing gestational hypertension. Mn modified the association with As such that the deleterious association with As was stronger at lower concentrations of Mn. First trimester urinary dimethylarsinic acid concentrations were not associated with gestational hypertension (RR=1.31; 95% CI: 0.60, 2.85) or preeclampsia (RR = 0.92; 95% CI: 0.68, 1.24). We did not observe overall joint effects for blood metals. Discussion: Our results confirm that even low blood Pb concentrations are a risk factor for preeclampsia. Women with higher blood As concentrations combined with lower Mn in early pregnancy were more likely to develop gestational hypertension. These pregnancy complications impact maternal and neonatal health. Understanding the contribution of toxic metals and Mn is of public health importance. https://doi.org/10.1289/EHP10825, Introduction Gestational hypertension and preeclampsia are major contributors to maternal (1,2) and newborn (3,4) morbidity and mortality. Women with these conditions have an increased risk of developing hypertension and other [...]

Abstract One of the biggest issues in civil engineering is the poor performance of concrete repairs. In fact, in Europe only 50% of concrete structures restorations are estimated to be successful, even though rehabilitation costs account for about half of the yearly construction budgets. This research aims at investigating a potential green approach to the sustainability of rehabilitation solutions for infrastructures. Following a simplified analysis of C02 emissions, intervention costs, social aspects, structural performances and other variables considered relevant to the scope, possible rehabilitation techniques are compared and ranked. The following four different options have therefore been designed to be applied to an actual column of the Brabau Bridge in Sardinia (Italy): i. complete removal and replacement of the column, ii. replacement of the damaged longitudinal rebars by machined bars and ultra-high performance fibre-reinforced concrete (UHPFRC) strengthening, iii. longitudinal and transverse fiber reinforced polymers (FRP) wrapping, iv. concrete jacketing. A methodological and procedural strategy is established through multi-criteria analysis that will allow future developments to assess the whole Life Cycle Assessment of the maintenance work.

Amphipods are widespread in the marine environment, and some have adopted a symbiotic lifestyle, such as numerous species of the genus Leucothoe (Leach, 1814). Unfortunately, few examples of such a relationship are known for the Mediterranean Sea. In the present study, we report for the first time the symbiotic relationship between Leucothoe richiardii (Lessona, 1865) and the ascidian Phallusia mammillata (Cuvier, 1815) from the Mar Grande of Taranto. Two samplings were carried out in November 2021 and May 2022, and the population structure of L. richiardii was also analyzed in relation to host weight. L. richiardii was found to live its entire cycle in P. mammillata. The amphipod population was dominated by females, and in most cases, juveniles of various sizes were found together with adults, indicating prolonged parental care. The host selection by the amphipods proved to be random and was determined by the abundance/availability of ascidians rather than their weight. The ascidians showed no signs of disturbance by the inhabiting amphipods, although they were present in large numbers, and we assumed that the relationship between L. richiardii and P. mammillata was commensal.

Animals that wield toxins face self-intoxication. Poison frogs have a diverse arsenal of defensive alkaloids that target the nervous system. Among them is epibatidine, a nicotinic acetylcholine receptor (nAChR) agonist that is lethal at microgram doses. Epibatidine shares a highly conserved binding site with acetylcholine, making it difficult to evolve resistance yet maintain nAChR function. Electrophysiological assays of human and frog nAChR revealed that one amino acid replacement, which evolved three times in poison frogs, decreased epibatidine sensitivity but at a cost of acetylcholine sensitivity. However, receptor functionality was rescued by additional amino acid replacements that differed among poison frog lineages. Our results demonstrate how resistance to agonist toxins can evolve and that such genetic changes propel organisms toward an adaptive peak of chemical defense.

BackgroundSocial anxiety disorder (SAD) is characterized by a significant amount of fear when confronted to social situations. Exposure therapy, which is based on fear extinction, does not often lead to full remission. Here, based on evidence showing that rapid eye movement (REM) sleep promotes the consolidation of extinction memory, we used targeted memory reactivation (TMR) during REM sleep to enhance extinction learning in SAD.MethodsForty-eight subjects with SAD were randomly assigned to two groups: control or TMR group. All patients had two successive exposure therapy sessions in a virtual reality (VR) environment, where they were asked to give a public talk in front of a virtual jury. At the end of each session, and only in the TMR group (N = 24), a sound was paired to the positive feedback phase of therapy (i.e., approval of their performance), which represented the memory to be strengthened during REM sleep. All participants slept at home with a wearable headband device which automatically identified sleep stages and administered the sound during REM sleep. Participants' anxiety level was assessed using measures of parasympathetic (root mean square of successive differences between normal heartbeats, RMSSD) and sympathetic (non-specific skin conductance responses, ns-SCRs) activity, and subjective measures (Subjective Units of Distress Scale, SUDS), during the preparation phase of their talks before (T1) and after (T2) one full-night's sleep and after 1 week at home (T3). Participants also filled in a dream diary.ResultsWe observed an effect of time on subjective measures of anxiety (SUDS). We did not find any difference in the anxiety levels of the two groups after 1 week of TMR at home. Importantly, the longer the total duration of REM sleep and the more stimulations the TMR group had at home, the less anxious (increased RMSSD) these participants were. Finally, fear in dreams correlated positively with ns-SCRs and SUDS at T3 in the TMR group.ConclusionTMR during REM sleep did not significantly modulate the beneficial effect of therapy on subjective anxiety. Yet, our results support that REM sleep can contribute to extinction processes and substantiate strong links between emotions in dreams and waking stress levels in these patients.

Purpose: The purpose of this study was to determine which intensities, patterns, and types of 24-h movement behaviors are most strongly associated with cardiometabolic risk factors among children. Methods: A total of 369 children aged 10–13 years were studied. Participants wore an Actical accelerometer and a Garmin Forerunner 220 Global Positioning System logger and completed an activity and sleep log for 7 days. Data from these instruments were combined to estimate average minute per day spent in 14 intensities, 11 types, and 14 patterns of movement. Body mass index, resting heart rate, and systolic blood pressure values were combined to create a cardiometabolic risk factor score. Partial least squares regression analysis was used to examine associations between the 39 movement behavior characteristics and the cardiometabolic risk factor score. The variable importance in projection (VIP) values were used to determine and rank important movement behavior characteristics. There was evidence of interaction by biological maturity, and the analyses were conducted separately in the 50% least mature and 50% most mature participants. Results: For the least biologically mature participants, fifteen of the 39 movement behavior characteristics had important VIP value scores; eight of these reflected movement intensities (particularly moderate and vigorous intensities), six reflected movement patterns, and one reflected a movement type. For the most mature participants, thirteen of the 39 movement behavior characteristics had important VIP value scores, with five reflecting intensities (particularly moderate and vigorous intensities), five reflecting patterns, and three reflecting types of movement. Conclusion: More than 12 movement behavior characteristics were associated with cardiometabolic risk factors within both the most and least mature participants. Movement intensities within the moderate and vigorous intensity ranges were the most consistent correlates of these risk factors.

Abstract Eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2), better known as PKR, plays a key role in the response to viral infections and cellular homeostasis by regulating mRNA translation. Upon binding dsRNA, PKR is activated through homodimerization and subsequent autophosphorylation on residues Thr446 and Thr451. In this study, we identified a novel PKR phosphorylation site, Ser6, located 3 amino acids upstream of the first double-stranded RNA binding motif (DRBM1). Another Ser residue occurs in PKR at position 97, the very same position relative to the DRBM2. Ser or Thr residues also occur 3 amino acids upstream DRBMs of other proteins such as ADAR1 or DICER. Phosphoinhibiting mutations (Ser-to-Ala) introduced at Ser6 and Ser97 spontaneously activated PKR. In contrast, phosphomimetic mutations (Ser-to-Asp) inhibited PKR activation following either poly (I:C) transfection or virus infection. These mutations moderately affected dsRNA binding or dimerization, suggesting a model where negative charges occurring at position 6 and 97 tighten the interaction of DRBMs with the kinase domain, thus keeping PKR in an inactive closed conformation even in the presence of dsRNA. This study provides new insights on PKR regulation mechanisms and identifies Ser6 and Ser97 as potential targets to modulate PKR activity for therapeutic purposes.

The infrastructure sector is paying increasing attention to sustainability. In particular, certain events have proven how preventive local interventions can save both user lives and the same infrastructures, thus highlighting the importance of maintenance. The ineffectiveness of concrete repairs is one of the main issues in civil engineering. Merely 50% of restoration operations on concrete buildings is considered to be effective in Europe, although rehabilitation costs cover nearly half of the annual construction investments. This study investigates a potential strategy to improve the sustainability of infrastructure restoration solutions. A simplified examination of CO2 emissions, intervention costs, social factors, structural performances, and other factors considered relevant for this research, is followed by a comparison and ranking of the potential rehabilitation solutions. Four approaches have been selected to design retrofit interventions on a real column of the Sardinian Brabau bridge in Italy: i) complete column replacement; ii) substitution of the damaged longitudinal rebars with machined bars and the casting of a new concrete cover in ultra-high performance fibre-reinforced concrete; iii) longitudinal and transverse fibrereinforced polymer wrapping; iv) concrete jacketing at the base. Through the application of selected criteria, a methodological and procedural approach is developed. It provides a tool for assessing the sustainability of infrastructure maintenance works throughout the entire life cycle in the subsequent phases of this research. [ABSTRACT FROM AUTHOR]

Abstract Harmonized institutional processes and reviewer training are vital to maintain integrity and ethical rigor of the veterinary clinical research pipeline and are a prerequisite to future work that might establish centralized or single-site ethical and regulatory review to ease initiation of multi-center studies. Funded by a CTSA One Health Alliance (COHA) pilot award, a diverse working group of veterinary clinicians and institutional representatives was convened in February 2020 to develop a guidance document detailing broadly agreed upon practices for ethical review and approval of veterinary clinical studies conducted in the United States. The working group defined key areas of need for consensus, developed a set of associated guidelines, and circulated these for review by COHA’s fifteen member institutions. Six focus areas were identified by the working group and included vital items of protocol review, composition of the review committee, post-approval monitoring and adverse event reporting, consideration of special circumstances such as satellite sites and the use of healthy veterinary subjects in research, and the informed consent process. This document outlines a broadly agreed-upon framework through which to approach vital items associated with veterinary clinical study protocol review and approval. These approaches represent current best practice in the review and approval of veterinary clinical studies, and can serve as a guidance for veterinary clinician-scientists and regulatory experts, to ensure robust and ethically conducted studies that can contribute to the advancement of both animal and human health.

Abstract Objective Expression of the translocator protein (TSPO) on inflammatory cells has facilitated imaging of synovitis with TSPO-targeted positron emission tomography (PET). We aimed to quantitatively assess the specificity of the second-generation TSPO PET radioligand, [11C]PBR28, and to generate simplified PET protocols in patients with inflammatory joint disease (IJD) in this pilot study. Methods Three IJD patients (two rheumatoid arthritis and one osteoarthritis) with knee involvement underwent dynamic [11C]PBR28-PET scans before and after administration of 90 mg of oral emapunil (XBD-173), a TSPO ligand the same day. Radial arterial blood sampling was performed throughout the scan, and total radioactivity and radioactive metabolites were obtained. A semi-automated method was used to generate regions of interest. Standardized uptake value (SUV) and SUV ratio corrected for activity in bone and blood between 50 and 70 min (SUVr50–70 bone, SUVr50–70 blood, respectively) and PET volume of distribution (V T) of the radioligand were calculated. Results A mean [11C]PBR28 radioactivity of 378 (range 362–389) MBq was administered. A significant decrease (p

The biodiversity of macrobenthic invertebrates of two artificial hard substrates close to a mariculture plant was assessed in order to understand the effect on the fouling community of an innovative Integrated Multi-Trophic Aquaculture (IMTA) system. The examined hard substrates were (i) vertical bare collectors that are placed around the cages as new colonizable substrates, which were investigated from the early colonization and (ii) artificial hard substrates already present under the cages analyzed over time to observe changes due to the action on the water column by filter feeder organisms colonizing the above vertical collectors. Overall, 186 taxa were collected (both the substrates), of which 99 as sessile habitat-former or structuring macroinvertebrates and 87 as associated fauna, mostly vagile forms. On the vertical collectors 121 taxa were collected, among which 44 sessile structuring species and 77 vagile-associated taxa; on the artificial hard substrates under the cages, 124 taxa were identified, 95 belong to the first category and 29 as associated taxa. The two analyzed substrates shared 43% of sessile species (40) and 22% of associated species (19). At the end of the first year of experimentation, the study revealed Sabella spallanzanii and mussels as the most abundant taxa. Lastly, the communities under the cages showed an increase in biodiversity after the placement of collectors. The changes were attributed to the decrease in particulate matter originating as wastes from the breeding cage, which was intercepted by the filter feeder community developed on the vertical collectors.