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    Adoptive transfer of RUPP NKs into Sham rats resulted in elevated NK activation, UARI, placental oxidative stress, and preproendothelin expression as well as reduced circulating nitrate/nitrite. This led to maternal hypertension and IUGR. RUPP recipients of Sham NKs demonstrated normalized NK activation, sFlt-1, circulating and placental VEGF, and UARI, which led to improved maternal blood pressure and normal fetal growth.

    These data suggest a direct role for cNKs in causing preeclampsia pathophysiology and a role for normal NKs to improve maternal outcomes and IUGR during late gestation.

    These data suggest a direct role for cNKs in causing preeclampsia pathophysiology and a role for normal NKs to improve maternal outcomes and IUGR during late gestation.Recent industrial developments have resulted in an increase in the use of so-called technology-critical elements (TCEs), for which the potential impacts on aquatic biota remain to be evaluated. In the present study, quantitative ion character-activity relationships (QICARs) have been developed to relate intrinsic metal properties to their toxicity toward freshwater aquatic organisms. In total, 23 metal properties were tested as predictors of acute median effect concentration (EC50) values for 12 data-rich metals, for algae, daphnids, and fish (with and without species distinction). Simple and multiple linear regressions were developed using the toxicological data expressed as a function of the total dissolved metal concentrations. The best regressions were then tested by comparing the predicted EC50 values for the TCEs (germanium, indium, gold, and rhenium) and platinum group elements (iridium, platinum, palladium, rhodium, and ruthenium) with the few measured values that are available. The 8 “best” QICAR models (adjusted r2  > 0.6) used the covalent index as the predictor. For a given metal ion, this composite parameter is a measure of the importance of covalent interactions relative to ionic interactions. Toxicity was reasonably well predicted for most of the TCEs, with values falling within the 95% prediction intervals for the regressions of the measured versus predicted EC50 values. Exceptions included Au(I) (all test organisms), Au(III) (algae and fish), Pt(II) (algae, daphnids), Ru(III) (daphnids), and Rh(III) (daphnids, fish). We conclude that QICARs show potential as a screening tool to review toxicity data and flag “outliers,” which might need further scrutiny, and as an interpolating or extrapolating tool to predict TCE toxicity. Environ Toxicol Chem 2021;401139-1148. © 2020 SETAC.

    Patient safety within dental education is paramount. Wrong-site surgery (WSS) tooth extraction is not uncommon and is a significant never event (NE) in dentistry. This study aimed to explore dental schools’ undergraduate experience of NEs, safety interventions implemented and the impact on student experience.

    All 16 UK dental schools were surveyed via email.

    The response rate was 100%. A modified World Health Organization (WHO) checklist was used within institutions (94%) including pre-operative briefings and recording teeth on whiteboards (81%, respectively). Students were directly supervised performing extractions (63%) utilising a 14 staff student ratio. WSS by students was reported in 69% of schools, with student experience being impacted by an increased patient safety focus.

    This study demonstrated an increased utilisation of an adapted WHO checklist. Modification of practices to ensure patient safety was demonstrated at all schools, irrespective of student WSS occurrences. Institutions experiencs resulted in reduced student clinical experience. A proposed minimum standard for undergraduate surgery is suggested to ensure safe and competent dental practitioners of the future.

    Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, exerts multiple protective effects against cardiovascular diseases, including cardiac hypertrophy. However, the molecular mechanism underlying its anti-hypertrophic effect has not been clarified. This study revealed that EGCG could inhibit pressure overload-induced cardiac hypertrophy by regulating the PSMB5/Nmnat2/SIRT6-dependent signalling pathway.

    Quantitative real-time polymerase chain reaction and western blotting were used to determine the expression of mRNA and protein respectively. A fluorometric assay kit was used to determine the activity of SIRT6, a histone deacetylase. Luciferase reporter gene assay and electrophoretic mobility shift assay were employed to measure transcriptional activity and DNA binding activity respectively.

    EGCG could significantly increase Nmnat2 protein expression and enzyme activity in cultured neonatal rat cardiomyocytes stimulated with angiotensin II (Ang II) and heart tissues from rats subjesuggesting the therapeutic potential of EGCG in the prevention and treatment of cardiac hypertrophy.

    Cardiac allograft vasculopathy (CAV) and nephrotoxicity affect long-term survival after heart transplantation (HTX). Studies, mostly conducted in adults, showed a positive effect of everolimus (EVL) on these problems. We describe the effects of conversion of the immunosuppressive therapy to an everolimus including regime on CAV, renal function, and safety in heart transplanted children/adolescents.

    This retrospective single-center study included 36 participants (mean time after HTX 6.3±4.7years). Descriptive pre/post-comparisons were performed with an observation period partially up to 4years. Impact on CAV was assessed based on intravascular imaging and Stanford grading. Safety analysis included cytomegalovirus (CMV)-infection and acute rejection.

    In terms of CAV (9 out of 36 patients) four showed no progression, three an improvement, one a worsening; one new diagnosis. The average CrCl showed a significant improvement 6, 12, and 24months after conversion regarding all patients (n=29). There was no acute rejection or CMV-infection.

    Conversion to an EVL-based therapy after pediatric HTX is a safe immunosuppressive regime without increasing risk of acute rejection or CMV-infection. There was some evidence of reduction in progression of CAV and a significant improvement of the renal function.

    Conversion to an EVL-based therapy after pediatric HTX is a safe immunosuppressive regime without increasing risk of acute rejection or CMV-infection. There was some evidence of reduction in progression of CAV and a significant improvement of the renal function.Hippocampal volume is a marker of brain health and is reduced with aging and neurological disease. Exercise may be effective at increasing and preserving hippocampal volume, potentially serving as a treatment for conditions associated with hippocampal atrophy (e.g., dementia). This meta-analysis aimed to identify whether exercise training has a positive effect on hippocampal volume and how population characteristics and exercise parameters moderate this effect. Studies met the following criteria (a) controlled trials; (b) interventions of physical exercise; (c) included at least one time-point of hippocampal volume data before the intervention and one after; (d) assessed hippocampal volume using either manual or automated segmentation algorithms. Animal studies, voxel-based morphometry analyses, and multi-modal interventions (e.g., cognitive training or meditation) were excluded. The primary analysis in n = 23 interventions from 22 published studies revealed a significant positive effect of exercise on total hippocampal volume. The overall effect was significant in older samples (65 years of age or older) and in interventions that lasted over 24 weeks and had less than 150 min per week of exercise. These findings suggest that moderate amounts of exercise for interventions greater than 6 months have a positive effect on hippocampal volume including in older populations vulnerable to hippocampal atrophy.The liver is the main organ responsible for drug and xenobiotic metabolism and detoxification in the body. There are many antiepileptic drugs and nanoparticles that have been reported to cause serious untoward biological responses and hepatotoxicity. The aim of this study is to investigate the potential toxic effect of aspartic acid-coated magnesium oxide nanoparticles (Mg nano) and valproate (valp) using an in vitro three-dimensional (3D) human liver organoid model and an in vivo pentylenetetrazole (PTZ)-induced convulsion model in rats. Here, 3D human liver organoids were treated with valp or valp + Mg nano for 24 h and then incubated with PTZ for an extra 24 h. As the in vivo model, rats were treated with valp, Mg nano, or valp + Mg nano for 4 weeks and then they were treated with PTZ for 24 h. Toxicity in the liver organoids was demonstrated by reduced cell viability, decreased ATP, and increased reactive oxygen species. In the rat convulsion model, results revealed elevated serum alanine aminotransferase and aspartate aminotransferase levels. Both the in vitro and in vivo data demonstrated the potential toxic effects of valp + Mg nano on the liver tissues.Shoreline spiders have been proposed as sentinels to monitor aquatic contaminants including methylmercury (MeHg). The present study examined the effect of spider body size on MeHg concentrations in shoreline spiders. We collected 6 taxa of spiders belonging to 4 families (orb-weavers [Araneidae], long-jawed orb weavers [Tetragnathidae Tetragnatha sp.], jumping spiders [Salticidae], and wolf spiders [Lycosidae Pardosa sp., Rabidosa sp., and Schizocosa sp.]) from the shorelines of 14 human-made ponds at the Lyndon B. Johnson National Grasslands in north Texas (USA). As a proxy for body size, we measured leg length (tibia + patella) of each spider. Spider taxa differed by 3-fold in mean MeHg concentration, and MeHg concentrations in 4 of 6 spider taxa increased significantly with leg length. The present study is the first to demonstrate that shoreline spider MeHg concentrations increase as a function of spider body size. Clofarabine Because spider size may account for some within-taxa variation in MeHg concentrations, future studies that utilize spiders as sentinels of aquatic contamination by MeHg or other biomagnifying contaminants should take spider size into account. Environ Toxicol Chem 2021;401149-1154. © 2020 SETAC.The objective of the present study was to evaluate the renal function of rural workers in a city of northeastern Brazil. A cross-sectional study was carried out with 208 workers in Boquim, Sergipe, Brazil. Renal function markers and butyrylcholinesterase (BChE) were evaluated and the glomerular filtration rate (GFR) was determined. The sample consisted mainly of illiterate males with a low usage of personal protective equipment and no training. Approximately 40% had some level of renal failure. Relative risk (1.59) of GFR alteration was higher in workers with more than 5 yr of exposure, mainly to organophosphates. Workers more than 60 yr of age presented a 17.06 greater risk for manifesting acute intoxication. Butyrylcholinesterase reduction was associated with reports of intoxication (relative risk of 11.36). We concluded that exposure to pesticides represented a risk factor for the development of nephrotoxic effects and alteration of renal function, which reinforced the need to implement measures to protect rural workers.