Project description:The aim was to evaluate in vitro cytotoxicity and genotoxicity of Bio-C Repair (BCR), compared to Endosequence BC Root Repair (ERRM), MTA Angelus (MTA-Ang), and MTA Repair HP (MTA-HP). MC3T3 osteoblastic cells were exposed to extracts of the repairing bioceramic cements. After 1, 3, and 7 days, cytotoxicity and genotoxicity were evaluated by MTT and Micronucleus tests, respectively. Cells not exposed to biomaterials were used as a negative control. Data were compared using ANOVA two-way, followed by the Tukey Test (α=5%). MTA-Ang and MTA-HP showed no difference in relation to control regarding cytotoxicity in any experimental times. BCR and ERRM reduced cell viability after 3 and 7 days (p<0.05); however, the reduction caused by BCR was less than that caused by ERRM. Considering the micronucleus formation, all biomaterials caused an increase after 3 and 7 days (p<0.05), being greater for the BCR and ERRM groups. It can be concluded that BCR is non-cytotoxic in osteoblastic cells, as well as MTA-Ang e MTA Repair HP. BCR and ERRM showed greater genotoxicity than others tested biomaterials.
Project description:With 300,000,000 riders annually, roller coasters are a popular recreational activity. Although the number of roller coaster injuries is relatively low, the precise effect of roller coaster rides on our brains remains unknown. Here we present the quantitative characterization of brain displacements and deformations during roller coaster rides. For two healthy adult male subjects, we recorded head accelerations during three representative rides, and, for comparison, during running and soccer headers. From the recordings, we simulated brain displacements and deformations using rigid body dynamics and finite element analyses. Our findings show that despite having lower linear accelerations than sports head impacts, roller coasters may lead to brain displacements and strains comparable to mild soccer headers. The peak change in angular velocity on the rides was 9.9 rad/sec, which was higher than the 5.6 rad/sec in soccer headers with ball velocities reaching 7 m/sec. Maximum brain surface displacements of 4.0 mm and maximum principal strains of 7.6% were higher than in running and similar to soccer headers, but below the reported average concussion strain. Brain strain rates during roller coaster rides were similar to those in running, and lower than those in soccer headers. Strikingly, on the same ride and at a similar position, the two subjects experienced significantly different head kinematics and brain deformation. These results indicate that head motion and brain deformation during roller coaster rides are highly sensitive to individual subjects. Although our study suggests that roller coaster rides do not present an immediate risk of acute brain injury, their long-term effects require further longitudinal study.
Project description:This study was designed to gain insight about the mechanisms involved in the anti-tumor effects of mithramycin A (MTA) and the MTA analog EC-8042 in sarcoma cells. In addition, we also studied whether this molecular features could be influenced by the nano-encapsulation of MTA.
Project description:Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA. However, MTA proteins interact with a variety of chromatin remodeling factors and complexes with enzymatic activities for modulating the plasticity of nucleosomes, leading to the repression or derepression of target genes or other extra-nuclear and nucleosome remodeling and histone deacetylase (NuRD)-complex independent activities. The functions of MTA family members are driven by the steady state levels and subcellular localization of MTA proteins, the dynamic nature of modifying signals and enzymes, the structural features and post-translational modification of protein domains, interactions with binding proteins, and the nature of the engaged and resulting features of nucleosomes in the proximity of target genes. In general, MTA1 and MTA2 are the most upregulated genes in human cancer and correlate well with aggressive phenotypes, therapeutic resistance, poor prognosis and ultimately, unfavorable survival of cancer patients. Here we will discuss the structure, expression and functions of the MTA family of genes in the context of cancer cells.
Project description:Encouraging routine COVID-19 vaccinations is likely to be a crucial policy challenge for decades to come. To avert hundreds of thousands of unnecessary hospitalizations and deaths, adoption will need to be higher than it was in the autumn of 2022 or 2023, when less than one-fifth of Americans received booster vaccines1,2. One approach to encouraging vaccination is to eliminate the friction of transportation hurdles. Previous research has shown that friction can hinder follow-through3 and that individuals who live farther from COVID-19 vaccination sites are less likely to get vaccinated4. However, the value of providing free round-trip transportation to vaccination sites is unknown. Here we show that offering people free round-trip Lyft rides to pharmacies has no benefit over and above sending them behaviourally informed text messages reminding them to get vaccinated. We determined this by running a megastudy with millions of CVS Pharmacy patients in the United States testing the effects of (1) free round-trip Lyft rides to CVS Pharmacies for vaccination appointments and (2) seven different sets of behaviourally informed vaccine reminder messages. Our results suggest that offering previously vaccinated individuals free rides to vaccination sites is not a good investment in the United States, contrary to the high expectations of both expert and lay forecasters. Instead, people in the United States should be sent behaviourally informed COVID-19 vaccination reminders, which increased the 30-day COVID-19 booster uptake by 21% (1.05 percentage points) and spilled over to increase 30-day influenza vaccinations by 8% (0.34 percentage points) in our megastudy. More rigorous testing of interventions to promote vaccination is needed to ensure that evidence-based solutions are deployed widely and that ineffective but intuitively appealing tools are discontinued.
Project description:Do people derive more enjoyment from activities that match how they ideally want to feel (their "ideal affect")? Affect valuation theory (AVT) predicts that they do; however, no study has directly examined whether this is the case. Therefore, the authors conducted 4 studies that examined whether valuing calm and other low arousal positive states (LAP) increased enjoyment of calming (vs. exciting) activities. In Study 1, the more participants valued LAP, the more enjoyment they recalled during calming (vs. exciting) episodes from their lives. In Studies 2-3, the more participants valued LAP, the more enjoyment they experienced during calming (vs. exciting) amusement park rides, both in the United States and Hong Kong. To assess causality, in Study 4, participants were randomly assigned to either a "value LAP" or control condition and then engaged in either low or high intensity exercise. Participants in the value LAP condition who engaged in low intensity exercise reported greater enjoyment than those who engaged in high intensity exercise; these differences did not emerge in the control condition. People's trait levels of experienced LAP ("actual LAP") were not related to their enjoyment of calming (vs. exciting) activities. Together, these findings provide evidence that people derive more enjoyment from activities that match their ideal affect. The authors discuss the implications of these findings for AVT as well as interventions aimed at enhancing well-being. (PsycINFO Database Record
Project description:High elimination rates and the concern for horse welfare are important issues in endurance riding. An improved understanding of the causes of elimination could increase completion rates in this sport. We have identified pre-ride risk factors that allow an assessment of potential elimination before the ride. A longitudinal cohort study was performed among 49 healthy horses competing in the 160 km endurance ride at the 2016 World Championship of Endurance Riding in Samorin/Slovakia. Blood samples were drawn before the ride. For statistical evaluation, horses were categorized in three groups: finishers, lame and metabolically eliminated horses. Risk factors were calculated for each group using multinomial logistic regression. A 1% increase in hematocrit levels was associated with a higher OR for elimination (lameness: OR 1.26, p = 0.017; metabolic: OR 1.34, p = 0.010). Furthermore, increased potassium values correlated negatively with the race outcome. For a 1 mmol/l increase in potassium, the lameness OR was 4.21, p = 0.039 and metabolic OR was 1.15, p = 0.848. Eight-year-old horses had a 100% elimination rate and survival analyses showed a significantly higher hazard for elimination (p = 0.025). We thus conclude that age and hydration affect the outcome of elite endurance rides. Further investigation of age as a risk factor seems to be clinically relevant and adjustments of FEI qualification modes may be appropriate.
Project description:Mineral trioxide aggregate (MTA) has been a revolutionary material in endodontics. Since its introduction in the 1990s several studies have demonstrated its use in various clinical applications. MTA has been extensively studied and is currently used for perforation repairs, apexifications, regenerative procedures, apexogenesis, pulpotomies, and pulp capping. This article will review the history, composition, research findings, and clinical applications of this versatile endodontic material.
Project description:Deletion of the MTAP gene leads to accumulation of the substrate of the MTAP protein, methylthioadenosine (MTA). MTA binds PRMT5 competitively with S-adenosyl-l-methionine (SAM), and selective inhibition of the PRMT5•MTA complex relative to the PRMT5•SAM complex can lead to selective killing of cancer cells with MTAP deletion. Herein, we describe the discovery of novel compounds using structure-based drug design to switch the mechanism of binding of known, SAM-cooperative PRMT5 inhibitors to an MTA-cooperative binding mechanism by occupying the portion of the SAM binding pocket in PRMT5 that is unoccupied when MTA is bound and hydrogen bonding to Arg368, thereby allowing them to selectively target MTAP-deleted cancer cells.