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In the present study we synthesized new methoxy derivatives of trans 2,3-diaryl-2,3-dihydrobenzofurans, starting from suitable trans 2,3-diaryloxiranes, using regio- and stereoselective nucleophilic oxiranyl ring-opening reactions. The compounds were tested as anti-inflammatories in U937 cells. All compounds showed a significant role in inhibiting the NF-κB pathway and were able to restore normal ROS and NO level upon LPS activation. Moreover, regarding inhibition of ACLY, enantioenriched (50% ee) 7a50 showed more potency than the racemic counterpart 7arac, together with a higher reduction of prostaglandin E2 production, thus suggesting a stereoselective interaction in this pathway.This study determines whether COVID-related risk-taking behavior was different among Republicans, Democrats, and Independents, in adults with elevated chance of severe complications from COVID-19. Using US national survey data collected September 30-October 27, 2020 (N = 6095), behaviors in the prior week examined were 7 potentially risky activities, mask wearing anywhere, and mask wearing while undertaking each activity. Differences among political affiliations were estimated for adults with 0 and with ≥1 medical risk factors for severe complications, adjusting for sociodemographic factors. Among adults with medical risk factors, the adjusted number of potentially risky activities was higher among Republicans (3.83) but not Independents (3.17) relative to Democrats (2.98). The adjusted percentage of adults with medical risk factors who wore a mask anywhere in the past week was lower for Republicans (87%) and Independents (91%) than for Democrats (97%). While undertaking each specific activity, the adjusted percentage of at-risk adults never wearing a mask was higher for Republicans than Democrats 24% vs 8% at bar/club; 6% vs 0% at grocery/pharmacy; 63% vs 30% visiting at friend's home; 68% vs 41% hosting visitors; 30% vs 5% at gathering of ≥10 people; 25% vs 11% while within 6 ft of someone they do not live with. Rates of mask wearing among political Independents were between rates among Democrats and Republicans. Efforts to reduce COVID-related risky behavior should recognize that although Republicans take more risks, rates of mask wearing at common activities are low across political affiliations, even for populations vulnerable to severe complications.Studies which examined the association between sedentary behavior (SB) and cognitive function have presented equivocal findings. Mentally active/inactive sedentary domains may relate differently to cognitive function. We examined associations between SB and cognitive function, specifically focusing on different domains. Participants were recruited from the Nijmegen Exercise Study 2018 in the Netherlands. SB (h/day) was measured with the Sedentary Behavior Questionnaire. Cognitive function was assessed with a validated computer self-test (COST-A), and a z-score calculated for global cognitive function. Multivariate linear regression assessed associations between tertiles of sedentary time and cognitive function. Cognition tests were available from 2821 participants, complete data from 2237 participants (43% female), with a median age of 61 [IQR 52-67] and a mean sedentary time of 8.3 ± 3.2 h/day. In fully adjusted models, cognitive function was significantly better in participants with the highest total sedentary time (0.07 [95% CI 0.02-0.12], P = 0.01), work-related sedentary time (0.13 [95% CI 0.07-0.19], P 0.05). We found a strong, independent positive association between total SB and cognitive function in a heterogenous population. This relation was not consistent across different domains, with especially work- and computer-related SB being positively associated with cognitive function. This highlights the importance of assessing the various sedentary domains in understanding the relation between sedentary time and cognitive function.High acceptance of coronavirus disease 2019 (COVID-19) vaccines is instrumental to ending the pandemic. Vaccine acceptance by subgroups of the population depends on their trust in COVID-19 vaccines. We surveyed a probability-based internet panel of 7832 adults from December 23, 2020-January 19, 2021 about their likelihood of getting a COVID-19 vaccine and the following domains of trust an individual's generalized trust, trust in COVID-19 vaccine's efficacy and safety, trust in the governmental approval process and general vaccine development process for COVID-19 vaccines, trust in their physician about COVID-19, and trust in other sources about COVID-19. We included identified at-risk subgroups healthcare workers, older adults (65-74-year-olds and ≥ 75-year-olds), frontline essential workers, other essential workers, and individuals with high-risk chronic conditions. Of 5979 respondents, only 57.4% said they were very likely or somewhat likely to get a COVID-19 vaccine. More hesitant respondents (p less then 0.05) included women, young adults (18-49 years), Blacks, individuals with lower education, those with lower income, and individuals without high-risk chronic conditions. selleck chemical Lack of trust in the vaccine approval and development processes explained most of the demographic variation in stated vaccination likelihood, while other domains of trust explained less variation. We conclude that hesitancy for COVID-19 vaccines is high overall and among at-risk subgroups, and hesitancy is strongly tied to trust in the vaccine approval and development processes. Building trust is critical to ending the pandemic.
This study assessed the margins needed to cover tumor intrafraction motion during an MR-guided radiotherapy (MRgRT) dose-escalation strategy in intermediate risk rectal cancer.
Fifteen patients with rectal cancer were treated with neoadjuvant short-course radiotherapy, 5x5 Gy, according to an online adaptive workflow on a 1.5T MR-linac. Per patient, 26 3D T2 weighted MRIs were made; one reference scan preceding treatment and five scans per treatment fraction. The primary tumor was delineated on each scan as gross tumor volume (GTV). Target coverage margins were assessed by isotropically expanding the reference GTV until more than 95% of the voxels of the sequential GTVs were covered. A margin with a coverage probability threshold of 90% was defined as adequate. Intra- and interfraction margins to cope with the movement of the GTV in the period between scans were calculated to indicate the target volume margins. Furthermore, the margin needed to cover GTV movement was calculated for different time intervals.
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