Δ9-tetrahydrocannabinol (THC) vapor exposure produces conditioned rewarding effects in male and female rats

Background: Vaping of cannabis and cannabis extracts containing Δ9-tetrahydrocannabinol (THC, the primary psychoactive constituent of cannabis) is on the rise. Development of animal models using vapor exposure is important for increasing our understanding of the rewarding and aversive effects of vaped cannabinoids. Currently there are limited data on the conditioned rewarding effects of THC vapor in rats, and no studies to date examining sex differences. Methods: Male and female Sprague-Dawley rats (N=96; 12 per sex/group) underwent place conditioning after exposure to vaporized THC or vehicle (propylene glycol, PG). THC vapor-conditioned rats received one of three THC vapor exposure amounts (THC Group 1: 5 puffs of 100 mg/ml THC, THC Group 2: 5 puffs of 200 mg/ml THC, or THC Group 3: 10 puffs of 200 mg/ml THC) and matched vehicle vapor (PG) exposure and on alternate days for two sets of 8 daily sessions (16 days total). Vehicle-conditioned rats (Veh Group 0) received only PG vapor exposure each day. Rats were passively administered vapor for 30-min immediately before daily, 30-min conditioning sessions. Untreated rats completed place preference tests after the 8th and 16th conditioning sessions and then testing continued daily until extinction occurred. Following extinction, rats underwent a THC vapor-primed reinstatement session. Results: Male and female rats showed an exposure-dependent preference for the THC vapor-paired chamber, though sex differences were observed. The lowest THC vapor exposure group tested (THC Group 1) did not produce CPP in males or females. Exposure to the middle condition tested (THC Group 2) resulted in preference for the THC vapor-paired chamber in males, but not females. The highest THC vapor exposure condition tested (THC Group 3) produced place preference in both males and females. Preference for the THC-paired chamber extinguished more quickly in males than in females. Following extinction, THC vapor re-exposure (i.e., drug-prime) did not result in reinstatement of place preference for either sex. Conclusion: This study demonstrated conditioned rewarding effects of THC vapor in both male and female rats, and provides evidence for sex differences in doses of THC vapor that produce CPP and in time to extinction. Conditioned place aversion was not observed at any of the THC vapor exposure amounts tested. These data provide a foundation for future exploration of the conditioned rewarding effects vaporized THC, cannabis and its constituents in preclinical models.

Differential Effect of SARS-CoV-2 Spike Glycoprotein 1 on Human Bronchial and Alveolar Lung Mucosa Models: Implications for Pathogenicity

Background: The SARS-CoV-2 spike protein mediates attachment of the virus to the host cell receptor and fusion between the virus and the cell membrane. The S1 subunit of the spike glycoprotein (S1 protein) contains the angiotensin converting enzyme 2 (ACE2) receptor binding domain. The SARS-CoV-2 variants of concern contain mutations in the S1 subunit. The spike protein is the primary target of neutralizing antibodies generated following infection, and constitutes the viral component of mRNA-based COVID-19 vaccines. Methods: Therefore, in this work we assessed the effect of exposure (24 h) to 10 nM SARS-CoV-2 recombinant S1 protein on physiologically relevant human bronchial (bro) and alveolar (alv) lung mucosa models cultured at air–liquid interface (ALI) (n= 6 per exposure condition). Corresponding sham exposed samples served as a control. The bro-ALI model was developed using primary bronchial epithelial cells and the alv-ALI model using representative type II pneumocytes (NCI-H441). Results: Exposure to S1 protein induced the surface expression of ACE2, toll like receptor (TLR) 2, and TLR4 in both bro-ALI and alv-ALI models. Transcript expression analysis identified 117 (bro-ALI) and 97 (alv-ALI) differentially regulated genes (p ≤ 0.01). Pathway analysis revealed enrichment of canonical pathways such as interferon (IFN) signaling, influenza, coronavirus, and anti-viral response in the bro-ALI. Secreted levels of interleukin (IL) 4 and IL12 were significantly (p < 0.05) increased, whereas IL6 decreased in the bro-ALI. In the case of alv-ALI, enriched terms involving p53, APRIL (a proliferation-inducing ligand) tight junction, integrin kinase, and IL1 signaling were identified. These terms are associated with lung fibrosis. Further, significantly (p < 0.05) increased levels of secreted pro-inflammatory cytokines IFNγ, IL1ꞵ, IL2, IL4, IL6, IL8, IL10, IL13, and tumor necrosis factor alpha were detected in alv-ALI, whereas IL12 was decreased. Altered levels of these cytokines are also associated with lung fibrotic response. Conclusions: In conclusion, we observed a typical anti-viral response in the bronchial model and a pro-fibrotic response in the alveolar model. The bro-ALI and alv-ALI models may serve as an easy and robust platform for assessing the pathogenicity of SARS-CoV-2 variants of concern at different lung regions.

Exposure Optimization Trial for Patients With Medical Implants During MRI Exposure: Balance Between the Completeness and Efficiency

Elongated conductors, such as pacemaker leads, can couple to the MRI radio-frequency (RF) field during MRI scan and cause dangerous tissue heating. By selecting proper RF exposure conditions, the RF-induced power deposition can be suppressed. As the RF-induced power deposition is a complex function of multiple clinical factors, the problem remains how to perform the exposure selection in a comprehensive and efficient way. The purpose of this work is to demonstrate an exposure optimization trail that allows a comprehensive optimization in an efficient and traceable manner. The proposed workflow is demonstrated with a generic 40 cm long cardio pacemaker, major components of the clinical factors are decoupled from the redundant data set using principle component analysis, the optimized exposure condition can not only reduce the in vivo power deposition but also maintain good image quality.

Personal narratives to improve attitudes towards stigmatized immigrants: A parallel-serial mediation model

This work addresses the study of factors that increase the persuasive efficacy of testimonial messages aimed at improving intergroup attitudes. The results of two online experiments ( N = 840) on the effect of empathy with, and similarity to, the protagonist in personal stories designed to improve attitudes towards immigrants are presented. In both studies, participants were given instructions to induce a certain exposure condition (empathy vs. an objective or distanced perspective) immediately before reading a narrative whose protagonist was an immigrant with high or low similarity to the audience. The results of mediation analysis show that both empathy and similarity increased identification and narrative transportation, which in turn reduced counterarguing, thus resulting in a more positive attitude towards the outgroup and lower threat perception. The results are discussed in the context of research on narrative persuasion and the design of campaigns to reduce racism and xenophobia.

Degradation of Shotcrete Materials Subjected to Sulfate and Chloride Attack in Varying Exposure Regimes

Durability of in situ shotcrete under external sulfate attack was investigated, taking into consideration the addition of mineral admixtures, along with the presence of chloride ions. Three water-to-binder ratios (w/b), i.e., 0.35, 0.45, and 0.55, and two types of supplementary cementitious materials (SCMs), namely, fly ash (FA) and silica fume (SF), were considered in the current study. Two different laboratorial immersion regimes (continuously full immersion and partial immersion with cycling temperature and relative humidity) were carried out to induce chemical/physical sulfate attack. Results show that loss of strength was the typical feature of chemical sulfate attack on shotcrete, while surface spalling dominated in deterioration caused by physical sulfate attack. The presence of chloride ions can globally mitigate these deteriorations. Meanwhile, the lower w/b ratio proved to be efficient in increasing the resistance to both sulfate attacks. Adding fly ash (FA) in shotcrete mixtures enhanced the long-term performance but invited massive white efflorescence on surface layer under partial-immersion exposure condition. Silica fume (SF) admixture can compensate the undesired reduction of early-age strength caused by FA addition, but make these specimens more susceptible to sulfate attack. Mercury intrusion porosimetry (MIP) analysis, scanning electron microscopy (SEM), and X-ray diffraction (XRD) tests reveal that these consequences were strongly related to the refinement of microstructure resulted from pozzolanic reactions and hydration kinetics.

Hypoxia-inducible transcription factor-1α inhibition by topotecan protects against lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes

Background Myocarditis, an inflammatory disease of the myocardium, is a serious hazard to human life due to the expansion of inflammatory lesions in the myocardium. The aim of this study was to investigate the role of hypoxia-inducible transcription factor (HIF)-1α and its inhibitor topotecan in the pathogenesis of myocarditis. Methods H9c2 cardiomyoblasts was stimulated with lipopolysaccharide (LPS) to simulate myocarditis model in vitro. The levels of myocardial damage markers were determined using commercially available kits. Western blotting was used to evaluate HIF-1α expression after LPS challenge. Then, after HIF-1α silencing, the contents of inflammatory factors were determined with enzyme-linked immunosorbent assay (ELISA). Cell viability was tested by means of a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed by flow cytometry, and the expression of apoptotic proteins was examined using western blot analysis. Subsequently, HIF-1α was overexpressed and topotecan was employed to treat H9c2 cells under LPS exposure condition. The biological functions were detected again. Results LPS significantly elevated the levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin-I (cTn-I) in supernatant of H9c2 cell lysates. Additionally, LPS led to the notably upregulated expression of HIF-1α. HIF-1α-knockdown markedly decreased the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 compared with the LPS-induced group. Moreover, the cell viability was conspicuously enhanced and cell apoptotic ratio was remarkably reduced, accompanied by downregulated expression of Bax, Bim, caspase 3 and caspase 9 after HIF-1α silencing. Consistently, HIF-1α gain-of-function significantly promoted the production of inflammatory cytokines and cell apoptosis, which was partially counteracted by topotecan administration. Conclusion To conclude, these findings demonstrated that HIF-1α inhibition by topotecan ameliorates LPS-induced myocarditis in vitro, providing a new approach in the treatment of myocarditis.

Chemical Composition of Gas and Particle Phase Products of Toluene Photooxidation Reaction under High OH Exposure Condition

In the current study, the photooxidation reaction of toluene (C7H8) was investigated in a Potential Aerosol Mass Oxidation Flow Reactor (PAM OFR). The hydroxyl radical (OH) exposure of toluene in the PAM OFR ranged from 0.4 to 1.4 × 1012 molec cm−3 s, which is equivalent to 3 to 12 days of atmospheric oxidation. A proton transfer reaction-mass spectrometer (PTR-MS) and a scanning mobility particle sizer (SMPS) were used to study the gas-phase products formed and particle number changes of the oxidation reaction in PAM OFR. The secondary organic aerosol (SOA) formed in the PAM OFR was also collected for off-line chemical analysis. Key gas-phase reaction products of toluene, including glyoxal, methyl glyoxal, unsaturated carbonyl compounds, and benzaldehyde, were identified by the PTR-MS. Second generation products, including acetic acid, formaldehyde, formic acid, and acetaldehyde, were also detected. By comparing the mass spectrums obtained under different OH exposures and relative humidity (RH), changes in the two parameters have minimal effects on the composition of gas-phase products formed, expect for the spectrum obtained at OH exposure of 0.4 × 1012 cm−3 s and RH = 17%, which is slightly different from other spectrums. SMPS results showed that particle mass concentration increases with increasing OH exposure, while particle number concentration first increases and then decreases with increasing OH exposure. This result probably suggests the formation of oligomers at high OH exposure conditions. Off-line chemical analysis of the SOA sample was dominated by C4 diacids, including malic acid, citramalic acid, and tartaric acid. The well-known toluene SOA marker 2,3-Dihydroxy-4-oxopentanoic acid, as well as 2,3-dihydroxyglutaric acid, which has not been identified in previous toluene photooxidation experiments, were also detected in the SOA sample. Our results showed good agreements with the results of previous smog chamber studies of toluene photooxidation reaction, and they suggested that using PAM OFR for studies of oxidation reaction of different VOCs can be atmospherically relevant.

Determination of Pendimethalin Dynamic Residual Distribution in Crucian Carp Tissues and Associated Risk Assessment

Pendimethalin has been considered a moderately to extremely toxic compound for fish and aquatic organism. This study developed the determination of dynamic residual distribution for pendimethalin in crucian carp tissues (muscle, liver, kidney, gill, and blood) under semistatic exposure system by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. The pendimethalin residues in various fish tissues increased initially and then decreased, and the residue amount of pendimethalin varied from tissue to tissue of crucian carp. Particularly, the pendimethalin accumulation in most fish tissues made significant decreases at two-time points. Pendimethalin was initially absorbed and enriched by fish body, and then partial pendimethalin was discharged into the outside environment through the metabolism function of crucian carp. The residue levels of pendimethalin distributed in crucian carp were ranked in the following decreasing order: liver > kidney > gill or muscle > blood, attributed to the fact that pendimethalin tends to accumulate in lipid-rich tissues of fish. Risk assessment results indicated that the chronic risk from dietary exposure to pendimethalin through crucian carp consumption for Chinese residents was acceptable, along with a lower estimated exposure dose (EED) than acceptable daily intake (ADI) and risk quotient (RQ) < 1. This study performed the first analysis for pendimethalin residual distribution in crucian carp tissues under semistatic exposure condition and provided a reference for pollution control and risk assessment of pendimethalin aimed at aquatic products.

Impact of Concrete Mix Ingredients and Surface Treatments on Epoxy Overlay Performance

Epoxy overlays are applied on bridge decks after curing concrete in patches and repairs for 28 days. A tensile bond pull-off strength of at least 250 pounds per square inch (psi) is expected from a properly applied overlay. Even though the overlay performance at room temperature is mostly satisfactory, the performance at elevated temperatures is not convincing. The degradation of mechanical and adhesion properties of epoxy, shear stress at the concrete/overlay interface caused by thermal incompatibility, and the interface moisture vapor pressure are the commonly cited parameters for poor bond strength at elevated temperatures. A combined effect of these parameters results in the most unfavorable failure mode (which is bond failure at the concrete/overlay interface) at a strength lower than the specified limit of 250 psi. The moisture migration through concrete depends on many factors including moisture content along the depth of concrete, pore microstructure, exposure condition, and drying period. This study investigated the impact of concrete mix ingredients and surface treatments on the thin epoxy overlay bond strength. The results show that the use of concrete mixes with slag and penetrating sealant pretreatment improves the bond strength.

Repetitive robot behavior impacts perception of intentionality and gaze-related attentional orienting.

Gaze behavior is an important social signal between humans, as it communicates locations of interest. People typically orient their attention to where others look, as this informs about others’ intentions and future actions. Studies have shown that humans can engage in similar gaze behavior with robots, but presumably more so when they adopt the intentional stance towards them (i.e., believing robot behaviors are intentional). In laboratory settings, the phenomenon of attending towards the direction of others’ gaze has been examined with the use of the gaze-cueing paradigm. While the gaze-cueing paradigm has been successful in investigating the relationship between adopting the intentional stance towards robots and attention orient-ing to gaze cues, it is unclear if the repetitiveness of the gaze-cueing paradigm influences adopting the intentional stance. Here, we examined if the duration of exposure to repetitive robot gaze behavior in a gaze-cueing task has a negative impact on subjective attribution of intentionality. Participants performed a short, medium, or long face-to-face gaze-cueing paradigm with an embodied robot while subjective ratings were collected pre and post the interaction. Results show that participants in the long exposure condition had the smallest change in their intention attribution scores, if any, while those in the short exposure condition had a positive change in their intention attribution indicating that participants attributed more intention to the robot after short interactions. The results also show that attention orienting to ro-bot gaze-cues was positively related to how much intention was attributed to the robot, but this relationship became more negative as the length of exposure increased. In contrast to subjective ratings, the gaze cueing effects increased as a function of the duration of exposure to repetitive behavior. The data suggest a tradeoff between the desired number of trials needed for observing various mechanisms of social cognition, such as gaze cueing effects, and the likelihood of adopting the intentional stance towards a robot.