Abnormal susceptibility to distracters hinders perception in early stage Parkinson's disease: a controlled study

BACKGROUND: One of the perceptual abnormalities observed in Parkinson's disease (PD) is a deficit in the suppression of reflexive saccades that are automatically triggered by the onset of a peripheral target. Impairment of substantia nigra function is thought to lead to this reduced ability to suppress reflexive saccades. METHODS: The present study examined whether this perceptual deficit is also present in early stage PD when using hardly noticeable task-irrelevant stimuli. Eleven non-demented de novo, untreated PD patients (mean age 57 yr, range 44 – 70) participated in the study as well as 12 age-matched controls. Performance on an 'oculomotor capture' task, in which in half of the trials an irrelevant stimulus with sudden onset was added to the display, was compared between patients and controls. Analysis of variance (ANOVA) was performed with group (patients/controls) and age (< 61 yrs/≥ 61 yrs) as independent factors and type of trial (control/distracter) as repeated measurements factor. The factor sex was used as covariate. RESULTS: With respect to Reaction Time (RT), a significant interaction between group and condition was found. RTs increased under the 'irrelevant stimulus' condition in both groups, the patients exhibiting a significantly larger increase in RTs than the control group. Also, a significant interaction effect between group and condition for number of correct responses was found. The number of correct responses was reduced in the onset distracter condition, the reduction being larger in the patients. In the patient group, contrary to the control group, a higher age was associated with fewer correct responses at baseline and in the onset distracter condition, suggesting that perceptual functions in PD are highly susceptible to the effects of ageing. The increased reaction times and larger number of incorrect responses of the PD patients in the onset distracter condition may be related to impairments of substantia nigra function and lower brain stem. CONCLUSION: The capture task seems to be a sensitive instrument to detect early perceptual deficits in PD. The magnitude of the observed deficits suggests that perceptual functions in early stage PD are so substantially impaired that this may interfere with daily activities

Novel test structures for temperature budget determination during wafer processing

Temperature is a crucial parameter in many planar technology processing steps. However, the determination of the actual temperature history at the device side of the substrate is not straightforward. We present a novel method for determining the temperature history of the process side of silicon wafers and chips, which is based on well-known silicide formation reactions of metal-Si systems and is determined via (4 point probe) resistance measurements. In this case we explored the Pd-Si system which has a suitable operating range from 100-200°C. We propose a method based on metal layers patterned in different line configurations (using the width and number of the lines as parameters) and anticipate that silicide developments at these structures is geometrically dependent and hence can provide a way for obtaining a refined temperature information. First experiments on bulk Si wafers show that the proposed method yields predictable and stable results

Double trouble: Co-infection of potato with the causal agents of late and early blight

Global potato production is plagued by multiple pathogens, amongst which are Phytophthora infestans and Alternaria solani, the causal agents of potato late blight and early blight, respectively. Both these pathogens have different lifestyles and are successful pathogens of potato, but despite observations of both pathogens infecting potato simultaneously in field conditions, the tripartite interactions between potato and these two pathogens are so far poorly understood. Here we studied the interaction of A. solani and P. infestans first in vitro and subsequently in planta both in laboratory and field settings. We found that A. solani can inhibit P. infestans in terms of growth in vitro and also infection of potato in both laboratory experiments and in an agriculturally relevant field setting. A. solani had a direct inhibitory effect on P. infestans in vitro and compounds secreted by A. solani had both an inhibitory and disruptive effect on sporangia and mycelium of P. infestans in vitro. In planta infection bioassays revealed that simultaneous co-inoculation of both pathogens resulted in larger necrotic lesions than single inoculations; however, consecutive inoculations only resulted in larger lesions when A. solani was inoculated after P. infestans. These results indicate that the order in which these pathogens attempt to colonize potato is important for the disease outcome and that the influence of plant pathogens on each other should be accounted for in the design of future disease control strategies in crops such as potato

Plasma amyloid-β levels, cerebral atrophy and risk of dementia: A population-based study

Background: Plasma amyloid-β (Aβ) levels are increasingly studied as a potential accessible marker of cognitive impairment and dementia. However, it remains underexplored whether plasma Aβ levels including the novel Aβ peptide 1-38 (Aβ1-38) relate to preclinical markers of neurodegeneration and risk of dementia. We investigated the association of plasma Aβ1-38, Aβ1-40, and Aβ1-42 levels with imaging markers of neurodegeneration and risk of dementia in a prospective population-based study. Methods: We analyzed plasma Aβ levels in 458 individuals from the Rotterdam Study. Brain volumes, including gray matter, white matter, and hippocampus, were computed on the basis of 1.5-T magnetic resonance imaging (MRI). Dementia and its subtypes were defined on the basis of internationally accepted criteria. Results: A total of 458 individuals (mean age, 67.8 ± 7.7 yr; 232 [50.7%] women) with baseline MRI scans and incident dementia were included. The mean ± SD values of Aβ1-38, Aβ1-40, and Aβ1-42 (in pg/ml) were 19.4 ± 4.3, 186.1 ± 35.9, and 56.3 ± 6.2, respectively, at baseline. Lower plasma Aβ1-42 levels were associated with smaller hippocampal volume (mean difference in hippocampal volume per SD decrease in Aβ1-42 levels, - 0.13; 95% CI, - 0.23 to - 0.04; p = 0.007). After a mean follow-up of 14.8 years (SD, 4.9; range, 4.1-23.5 yr), 79 persons developed dementia, 64 of whom were diagnosed with Alzheimer's disease (AD). Lower levels of Aβ1-38 and Aβ1-42 were associated with increased risk of dementia, specifically AD (HR for AD per SD decrease in Aβ1-38 levels, 1.39; 95% CI, 1.00-2.16; HR for AD per SD decrease in Aβ1-42 levels, 1.35; 95% CI, 1.05-1.75) after adjustment for age, sex, education, cardiovascular risk factors, apolipoprotein E ϵ4 allele carrier status, and other Aβ isoforms. Conclusions: Our results show that lower plasma Aβ levels were associated with risk of dementia and incident AD. Moreover, lower plasma Aβ1-42 levels were related to smaller hippocampal volume. These results suggest that plasma Aβ1-38 and Aβ1-42 maybe useful biomarkers for identification of individuals at risk of dementia

Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction

Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS) to glycolysis or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells, and little is known about the metabolic reprogramming of human microglia. In this study, we investigate the transcriptomic, proteomic, and metabolic profiles of mouse and iPSC-derived human microglia challenged with the TLR4 agonist LPS. We demonstrate that both species display a metabolic shift and an overall increased glycolytic gene signature in response to LPS treatment. The metabolic reprogramming is characterized by the upregulation of hexokinases in mouse microglia and phosphofructokinases in human microglia. This study provides a direct comparison of metabolism between mouse and human microglia, highlighting the species-specific pathways involved in immunometabolism and the importance of considering these differences in translational research.</p

Kinetics and 28-day test-retest repeatability and reproducibility of [C-11]UCB-J PET brain imaging

[C-11]UCB-J is a novel radioligand that binds to synaptic vesicle glycoprotein 2A (SV2A). The main objective of this study was to determine the 28-day test-retest repeatability (TRT) of quantitative [C-11]UCB-J brain positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients and healthy controls (HCs). Nine HCs and eight AD patients underwent two 60 min dynamic [C-11]UCB-J PET scans with arterial sampling with an interval of 28 days. The optimal tracer kinetic model was assessed using the Akaike criteria (AIC). Micro-/macro-parameters such as tracer delivery (K-1) and volume of distribution (V-T) were estimated using the optimal model. Data were also analysed for simplified reference tissue model (SRTM) with centrum semi-ovale (white matter) as reference region. Based on AIC, both 1T2k_V-B and 2T4k_V-B described the [C-11]UCB-J kinetics equally well. Analysis showed that whole-brain grey matter TRT for V-T, DVR and SRTM BPND were -2.2% +/- 8.5, 0.4% +/- 12.0 and -8.0% +/- 10.2, averaged over all subjects. [C-11]UCB-J kinetics can be well described by a 1T2k_V-B model, and a 60 min scan duration was sufficient to obtain reliable estimates for both plasma input and reference tissue models. TRT for V-T, DVR and BPND wa

Validation and test-retest repeatability performance of parametric methods for [11C]UCB-J PET

[(11)C]UCB-J is a PET radioligand that binds to the presynaptic vesicle glycoprotein 2A. Therefore, [(11)C]UCB-J PET may serve as an in vivo marker of synaptic integrity. The main objective of this study was to evaluate the quantitative accuracy and the 28-day test–retest repeatability (TRT) of various parametric quantitative methods for dynamic [(11)C]UCB-J studies in Alzheimer’s disease (AD) patients and healthy controls (HC). Eight HCs and seven AD patients underwent two 60-min dynamic [(11)C]UCB-J PET scans with arterial sampling over a 28-day interval. Several plasma-input based and reference-region based parametric methods were used to generate parametric images using metabolite corrected plasma activity as input function or white matter semi-ovale as reference region. Different parametric outcomes were compared regionally with corresponding non-linear regression (NLR) estimates. Furthermore, the 28-day TRT was assessed for all parametric methods. Spectral analysis (SA) and Logan graphical analysis showed high correlations with NLR estimates. Receptor parametric mapping (RPM) and simplified reference tissue model 2 (SRTM2) BP(ND), and reference Logan (RLogan) distribution volume ratio (DVR) regional estimates correlated well with plasma-input derived DVR and SRTM BP(ND). Among the multilinear reference tissue model (MRTM) methods, MRTM1 had the best correspondence with DVR and SRTM BP(ND). Among the parametric methods evaluated, spectral analysis (SA) and SRTM2 were the best plasma-input and reference tissue methods, respectively, to obtain quantitatively accurate and repeatable parametric images for dynamic [(11)C]UCB-J PET. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-021-00874-8

Early-stage [123I]beta-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson's disease

beta-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups. CONCLUSION: [(123)I]beta-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual case

Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences