Studying APOE ɛ4 Allele Dose Effects with a Univariate Morphometry Biomarker

Background: A univariate neurodegeneration biomarker (UNB) based on MRI with strong statistical discrimination power would be highly desirable for studying hippocampal surface morphological changes associated with APOE ɛ4 genetic risk for AD in the cognitively unimpaired (CU) population. However, existing UNB work either fails to model large group variances or does not capture AD induced changes. Objective: We proposed a subspace decomposition method capable of exploiting a UNB to represent the hippocampal morphological changes related to the APOE ɛ4 dose effects among the longitudinal APOE ɛ4 homozygotes (HM, N = 30), heterozygotes (HT, N = 49) and non-carriers (NC, N = 61). Methods: Rank minimization mechanism combined with sparse constraint considering the local continuity of the hippocampal atrophy regions is used to extract group common structures. Based on the group common structures of amyloid-β (Aβ) positive AD patients and Aβ negative CU subjects, we identified the regions-of-interest (ROI), which reflect significant morphometry changes caused by the AD development. Then univariate morphometry index (UMI) is constructed from these ROIs. Results: The proposed UMI demonstrates a more substantial statistical discrimination power to distinguish the longitudinal groups with different APOE ɛ4 genotypes than the hippocampal volume measurements. And different APOE ɛ4 allele load affects the shrinkage rate of the hippocampus, i.e., HM genotype will cause the largest atrophy rate, followed by HT, and the smallest is NC. Conclusion: The UMIs may capture the APOE ɛ4 risk allele-induced brain morphometry abnormalities and reveal the dose effects of APOE ɛ4 on the hippocampal morphology in cognitively normal individuals.

The Effect of Computerized Cognitive Training for Adults Over 40 with Dementia-Related Anxiety

Dementia-related anxiety (DRA) may occur when cognitive lapses are appraised as threatening. Individuals with DRA may seek activities to improve cognitive function, including popular computerized cognitive training programs like Lumosity©. We evaluated if DRA changed after eight weeks of Lumosity© use and whether changes were maintained over time. Participants aged 40 and older with pre-existing DRA participated via Amazon’s Mechanical Turk (T1 N = 395; age M = 52.49, SD = 8.71) and were randomly assigned to the experimental (Lumosity© software), active control (Lumosity© crossword puzzles), or no treatment group. Participants completed measures of DRA at T1 and at four follow-up points (T2 = 8 weeks; T3 = 12 weeks; T4 = 16 weeks; T5 = 20 weeks). Repeated measures ANOVAs were used to evaluate the change in DRA. A significant T1-T2 reduction in DRA occurred for the Lumosity© group only (p = .01, partial-eta2 = .03). Longitudinal changes were observed for the Lumosity© group only: DRA scores at T1 were significantly greater than at T2, T4, and T5 (ps < .05). A step-up test procedure was conducted to determine minimum treatment dose effects. A greater reduction in DRA occurred between the Lumosity© and crossword puzzle groups between 25.00 and 29.99 hours of software use (p = .05, partial-eta2 = .19). Lumosity© software outperformed crossword puzzles in DRA reduction from T1 to T2, which was maintained for 12 weeks post-software use. Independent of Lumosity’s intended purpose of supporting cognitive functioning, participants subjectively believe it helps and experience associated benefits.

Triadimefon in Aquatic Environments: Occurrence, Fate, Toxicity and Risk

Background：As a triazole fungicide, triadimefon is widely used around the world. The ubiquitous occurrence of triadimefon in aquatic environments and potential adverse effects on aquatic organisms have resulted in global concerns. In this review, the current state of knowledge on occurrence, environmental behavior, and toxic effects are presented and used to conduct an assessment of risks posed by current concentrations of triadimefon in aquatic environments. Results: The key findings from this review are that: (1) triadimefon occurred widely in surface waters, with high rates of detection; (2) abiotic degradation of triadimefon was affected by many factors. Stereo-selectivity was found during biotic degradation and metabolism of triadimefon. Different enantiomers can cause various adverse effects, which complicates the assessment and requires enantiomers-specific considerations; (3) triadimefon exposure can affect organisms by causing multiple toxic effects on the thyroid, reproduction system, liver, nervous system as well as carcinogenicity and teratogenicity, and it can also act synergistically with other pesticides. Long-term, low-dose effects were considered to be the main characteristics of toxic effects of triadimefon; (4) results of the risk assessment based on probabilistic relationships represented by Joint Probability Curves (JPCs) indicated that risk of triadimefon was classified as low risk.Conclusion: The concentration data of triadimefon in surface water is relatively less, more work needed to do to detect it. Reproductive toxicity was observed which indicated that triadimefon might result in adverse effects on the population level or even on the ecosystem level. Risk assessments for pesticides that cause long-term and low-dose effects on aquatic organisms such as triadimefon need to consider higher ecology level risk.

Dose-Effects Models for Space Radiobiology: An Overview on Dose-Effect Relationships

Space radiobiology is an interdisciplinary science that examines the biological effects of ionizing radiation on humans involved in aerospace missions. The dose-effect models are one of the relevant topics of space radiobiology. Their knowledge is crucial for optimizing radioprotection strategies (e.g., spaceship and lunar space station-shielding and lunar/Mars village design), the risk assessment of the health hazard related to human space exploration, and reducing damages induced to astronauts from galactic cosmic radiation. Dose-effect relationships describe the observed damages to normal tissues or cancer induction during and after space flights. They are developed for the various dose ranges and radiation qualities characterizing the actual and the forecast space missions [International Space Station (ISS) and solar system exploration]. Based on a Pubmed search including 53 papers reporting the collected dose-effect relationships after space missions or in ground simulations, 7 significant dose-effect relationships (e.g., eye flashes, cataract, central nervous systems, cardiovascular disease, cancer, chromosomal aberrations, and biomarkers) have been identified. For each considered effect, the absorbed dose thresholds and the uncertainties/limitations of the developed relationships are summarized and discussed. The current knowledge on this topic can benefit from further in vitro and in vivo radiobiological studies, an accurate characterization of the quality of space radiation, and the numerous experimental dose-effects data derived from the experience in the clinical use of ionizing radiation for diagnostic or treatments with doses similar to those foreseen for the future space missions. The growing number of pooled studies could improve the prediction ability of dose-effect relationships for space exposure and reduce their uncertainty level. Novel research in the field is of paramount importance to reduce damages to astronauts from cosmic radiation before Beyond Low Earth Orbit exploration in the next future. The study aims at providing an overview of the published dose-effect relationships and illustrates novel perspectives to inspire future research.