APOE genotype has been associated with various age-related outcomes including Alzheimers disease, frailty and mortality. In this study, the relationship between health, particularly cognitive function, and APOE was investigated in older men from the Concord Health and Ageing in Men Project (n=1616; age 76.9±5.5 yrs (range 70-97 yrs); Australia). Baseline characteristics and survival up to 12 years were determined. Frailty was measured using Cardiovascular Health study (CHS) criteria and Rockwood frailty index, and cognition using MiniMental State Examination (MMSE) and Addenbrookes Cognitive Examination. APOE ε4 was less common in the oldest men and those born in Mediterranean countries. APOE ε2 was beneficially associated with cholesterol, creatinine, gamma-glutamyl transaminase, glucose and HDL cholesterol while APOE ε4 was adversely associated with cholesterol and albumin. APOE ε4 was associated with a clinical diagnosis of Alzheimers disease when adjusted for age and region of birth (ε4 homozygotes OR 7.0; ε4 heterozygotes OR 2.4, P less then 0.05), and APOE ε2 had a small positive association with cognition. On multivariate regression, overall cognitive function in the entire cohort was associated with age, country of birth, education and frailty (all P less then 0.001). APOE was not associated with frailty or survival. In conclusion, age and region of birth influenced distribution of APOE genotype in older men. Although APOE ε4 was associated with Alzheimers disease, overall cognitive function in the cohort was associated more strongly with frailty than APOE genotype. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.The enzyme heme oxygenase-1 (HO-1), encoded by the HMOX1 gene, mediates heme catabolism by cleaving free heme. We have previously revealed the importance of HO-1 in pregnancy. Here, we determined the impact of maternal or paternal HO-1 deficiency on fetal growth and placental parameters throughout gestation. We mated Hmox1-sufficient (WT), partial (HET)- or total (KO)-deficient BALB/c female mice with Hmox1-WT or -KO BALB/c males and performed ultrasound analysis to monitor placental and fetal growth. Doppler measurements were used to determine maternal blood flow parameters. Offspring weights and feto-placental-indices (FPI) were also determined. We found a significantly increased number of underdeveloped fetuses at gd10 in HET females that were mated with WT males compared with WT x WT pairings. At the same gestational age, underdeveloped placentas could be detected in HET females mated with KO males.  https://www.selleckchem.com/products/myk-461.html  Many fetuses from the KO x KO combination died in utero between gd12 and gd14. At gd14, abnormal placental parameters were found in surviving fetuses, which had significant reduced weights. Moreover, only 3.11% female and 5.33% male KO pups resulted from ten HET x HET breeding pairs over one year. Our results show that HO-1 from both maternal and paternal origins is important for proper placental and fetal growth. Placental growth restriction and occurrence of abortions in mice that were partially or totally deficient in HO-1 were recorded in vivo from gd10 onwards. Future studies will focus on elucidating the cellular and molecular mechanisms behind these observations. © The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction.The purpose of this research was to investigate the impact of body mass index (BMI) on dose area product (DAP), effective dose (E), dose to the organs and image quality (IQ) on 200 patients referred to pelvic radiography. Patients were classified into three groups according to BMI normal (30). The results showed 52% and 135% higher DAP for overweight and obese patients compared to normal-weight patients (p  less then  0.001). A 46 and 123% rise of E for overweight and obese patients compared to normal-weight patients (p  less then  0.001) was discovered. Overweight patients received 37% higher dose and obese patients 107% higher dose to the organs compared to normal-weight patients. There were no statistically significant differences between IQ, except between normal weight and overweight patients. A strong correlation (r = 0.733) was found between BMI and DAP and between BMI and E (r = 0.776). © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.AMPA and NMDA receptors are ligand-gated ion channels that depolarize postsynaptic neurons when activated by the neurotransmitter L-glutamate. Changes in the distribution and activity of these receptors underlie learning and memory, but excessive change is associated with an array of neurological disorders, including cognitive impairment, developmental delay, and epilepsy. All of the ionotropic glutamate receptors (iGluRs) exhibit similar tetrameric architecture, transmembrane topology, and basic framework for activation; conformational changes induced by extracellular agonist binding deform and splay open the inner helix bundle crossing that occludes ion flux through the channel. NMDA receptors require agonist binding to all four subunits, whereas AMPA and closely related kainate receptors can open with less than complete occupancy. In addition to conventional activation by agonist binding, we recently identified two locations along the inner helix of the GluK2 kainate receptor subunit where cysteine (Cys) substitution yields channels that are opened by exposure to cadmium ions, independent of agonist site occupancy. Here, we generate AMPA and NMDA receptor subunits with homologous Cys substitutions and demonstrate similar activation of the mutant receptors by Cd. Coexpression of the auxiliary subunit stargazin enhanced Cd potency for activation of Cys-substituted GluA1 and altered occlusion upon treatment with sulfhydryl-reactive MTS reagents. Mutant NMDA receptors displayed voltage-dependent Mg block of currents activated by agonist and/or Cd as well as asymmetry between Cd effects on Cys-substituted GluN1 versus GluN2 subunits. In addition, Cd activation of each Cys-substituted iGluR was inhibited by protons. These results, together with our earlier work on GluK2, reveal a novel mechanism shared among the three different iGluR subtypes for prying open the gate that controls ion entry into the pore. © 2020 Wilding and Huettner.