Lack of mutagenic effect by multi-walled functionalized carbon nanotubes in the somatic cells of Drosophila melanogaster

AbstractCarbon nanotubes (CNTs) are formed by rolling up a single graphite sheet into a tube. Among the different types of CNTs, the multi-walled carbon nanotubes (MWCNTs) comprise a set of concentric nanotubes with perfect structures. Several uses for MWCNTs have been suggested to be included in biological applications such as manufacturing of biosensors, carriers of drugs. However, before these materials can be put on the market, it is necessary to know their genotoxic effects. Thus, this study aims to evaluate the mutagenicity of multi-walled carbon nanotubes (MWCNTs) functionalized in somatic cells of Drosophila melanogaster, using the somatic mutation and recombination test (SMART). This assay detects the loss of heterozygosity of marker genes expressed phenotypically on the wings of the fly. Larvae of three days were used, resulting from ST cross, with basal levels of the cytochrome P450 and larvae of high metabolic bioactivity capacity (HB cross). They were treated with different concentrations of MWCNTs functionalized. The MH descendants, analyzed in both ST and HB crosses, had no significant effects on the frequency of mutant. Based on the results and on the experimental conditions mentioned in this study, it was concluded that MWCNTs were not mutagenic in D. melanogaster

Epidemiology of autism spectrum disorder in Portugal: prevalence, clinical characterization, and medical conditions

The objective of this study was to estimate the prevalence of autistic spectrum disorder (ASD) and identify its clinical characterization, and medical conditions in a paediatric population in Portugal. A school survey was conducted in elementary schools, targeting 332,808 school-aged children in the mainland and 10,910 in the Azores islands. Referred children were directly assessed using the Diagnostic and Statistical Manual of Mental Disorders (4th edn), the Autism Diagnostic Interview-Revised, and the Childhood Autism Rating Scale. Clinical history and a laboratory investigation was performed. In parallel, a systematic multi-source search of children known to have autism was carried out in a restricted region. The global prevalence of ASD per 10,000 was 9.2 in mainland, and 15.6 in the Azores, with intriguing regional differences. A diversity of associated medical conditions was documented in 20%, with an unexpectedly high rate of mitochondrial respiratory chain disorders

Spatial-Temporal Patterns of Amyloid-β Accumulation: A Subtype and Stage Inference Model Analysis

BACKGROUND AND OBJECTIVES: Currently, amyloid-β (Aβ) staging models assume a single spatial-temporal progression of amyloid accumulation. We assessed evidence for Aβ accumulation subtypes by applying the data-driven Subtype and Stage Inference (SuStaIn) model to amyloid-PET data. METHODS: Amyloid-PET data of 3010 subjects were pooled from 6 cohorts (ALFA+, EMIF-AD, ABIDE, OASIS, and ADNI). Standardized uptake value ratios (SUVr) were calculated for 17 regions. We applied the SuStaIn algorithm to identify consistent subtypes in the pooled dataset based on the cross-validation information criterion (CVIC) and the most probable subtype/stage classification per scan. The effect of demographics and risk factors on subtype assignment was assessed using multinomial logistic regression. RESULTS: Participants were mostly cognitively unimpaired (N=1890, 62.8%), had a mean age of 68.72 (SD=9.1), 42.1% was APOE-ε4 carrier, and 51.8% was female. While a one-subtype model recovered the traditional amyloid accumulation trajectory, SuStaIn identified an optimal of three subtypes, referred to as Frontal, Parietal, and Occipital based on the first regions to show abnormality. Of the 788 (26.2%) with strong subtype assignment (>50% probability), the majority was assigned to Frontal (N=415, 52.5%), followed by Parietal (N=199, 25.3%), and Occipital subtypes (N=175, 22.2%). Significant differences across subtypes included distinct proportions of APOE-ε4 carriers (Frontal:61.8%, Parietal:57.1%, Occipital:49.4%), subjects with dementia (Frontal:19.7%, Parietal:19.1%, Occipital:31.0%) and lower age for the Parietal subtype (Frontal/Occipital:72.1y, Parietal:69.3y). Higher amyloid (Centiloid) and CSF p-tau burden was observed for the Frontal subtype, while Parietal and Occipital did not differ. At follow-up, most subjects (81.1%) maintained baseline subtype assignment and 25.6% progressed to a later stage. DISCUSSION: While a one-trajectory model recovers the established pattern of amyloid accumulation, SuStaIn determined that three subtypes were optimal, showing distinct associations to AD risk factors. Nonetheless, further analyses to determine clinical utility is warranted

Description of a European memory clinic cohort undergoing amyloid-PET: The AMYPAD Diagnostic and Patient Management Study

INTRODUCTION: AMYPAD Diagnostic and Patient Management Study (DPMS) aims to investigate the clinical utility and cost-effectiveness of amyloid-PET in Europe. Here we present participants' baseline features and discuss the representativeness of the cohort. METHODS: Participants with subjective cognitive decline plus (SCD+), mild cognitive impairment (MCI), or dementia were recruited in eight European memory clinics from April 16, 2018, to October 30, 2020, and randomized into three arms: ARM1, early amyloid-PET; ARM2, late amyloid-PET; and ARM3, free-choice. RESULTS: A total of 840 participants (244 SCD+, 341 MCI, and 255 dementia) were enrolled. Sociodemographic/clinical features did not differ significantly among recruiting memory clinics or with previously reported cohorts. The randomization assigned 35% of participants to ARM1, 32% to ARM2, and 33% to ARM3; cognitive stages were distributed equally across the arms. DISCUSSION: The features of AMYPAD-DPMS participants are as expected for a memory clinic population. This ensures the generalizability of future study results