Distinct amyloid-beta and tau-associated microglia profiles in Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent form of dementia and is characterized by abnormal extracellular aggregates of amyloid-beta and intraneuronal hyperphosphorylated tau tangles and neuropil threads. Microglia, the tissue-resident macrophages of the central nervous system (CNS), are important for CNS homeostasis and implicated in AD pathology. In amyloid mouse models, a phagocytic/activated microglia phenotype has been identified. How increasing levels of amyloid-beta and tau pathology affect human microglia transcriptional profiles is unknown. Here, we performed snRNAseq on 482,472 nuclei from non-demented control brains and AD brains containing only amyloid-beta plaques or both amyloid-beta plaques and tau pathology. Within the microglia population, distinct expression profiles were identified of which two were AD pathology-associated. The phagocytic/activated AD1-microglia population abundance strongly correlated with tissue amyloid-beta load and localized to amyloid-beta plaques. The AD2-microglia abundance strongly correlated with tissue phospho-tau load and these microglia were more abundant in samples with overt tau pathology. This full characterization of human disease-associated microglia phenotypes provides new insights in the pathophysiological role of microglia in AD and offers new targets for microglia-state-specific therapeutic strategies

Student Perception of Knowledge and Skills in Pharmacology and Pharmacotherapy in a Bachelor’s Medical Curriculum

Background: Pharmacology and pharmacotherapy (P&PT) is a foundational subject within the medical curriculum, preparing students for safe prescribing. The characteristics of students entering medical school change with time, and novel insights on teaching and learning also become available. A periodic review of the curriculum is required to investigate whether the current P&PT teaching optimally supports learning. Methods: To investigate this, the students’ perceptions of their knowledge and competence in various P&PT topics were studied. A total of 152 third-year bachelor’s students were invited to answer a 40-point online questionnaire. Results: The response rate for completing the questionnaire was 32% (N = 49). Students valued P&PT teaching, did not skip P&PT topics and desired more P&PT classes. Interestingly, students were hesitant to use recommended literature and textbooks to prepare themselves for classes. Concerning perceptions of knowledge and competence, students rated lower confidence in prescription writing skills and knowledge of drugs acting on the central nervous system. Conclusions: Although there are many positive elements within the current curriculum, the incorporation of teaching methodologies to ensure active student engagement is warranted. These modifications are essential to properly training the current generation of medical students for their role as future prescribers. A relatively low response rate and overestimation of one’s competencies remain potential biases in the study

Is EEG-biofeedback an effective treatment in autism spectrum disorders? A randomized controlled trial

Contains fulltext : 126000.pdf (publisher's version ) (Closed access)EEG-biofeedback has been reported to reduce symptoms of autism spectrum disorders (ASD) in several studies. However, these studies did not control for nonspecific effects of EEG-biofeedback and did not distinguish between participants who succeeded in influencing their own EEG activity and participants who did not. To overcome these methodological shortcomings, this study evaluated the effects of EEG-biofeedback in ASD in a randomized pretest-posttest control group design with blinded active comparator and six months follow-up. Thirty-eight participants were randomly allocated to the EEG-biofeedback, skin conductance (SC)-biofeedback or waiting list group. EEG- and SC-biofeedback sessions were similar and participants were blinded to the type of feedback they received. Assessments pre-treatment, post-treatment, and after 6 months included parent ratings of symptoms of ASD, executive function tasks, and 19-channel EEG recordings. Fifty-four percent of the participants significantly reduced delta and/or theta power during EEG-biofeedback sessions and were identified as EEG-regulators. In these EEG-regulators, no statistically significant reductions of symptoms of ASD were observed, but they showed significant improvement in cognitive flexibility as compared to participants who managed to regulate SC. EEG-biofeedback seems to be an applicable tool to regulate EEG activity and has specific effects on cognitive flexibility, but it did not result in significant reductions in symptoms of ASD. An important finding was that no nonspecific effects of EEG-biofeedback were demonstrated