Family screening for bicuspid aortic valve and aortic dilatation: a meta-analysis.

Aims: International guidelines recommend screening of first-degree relatives (FDR) of people with bicuspid aortic valves (BAVs). However, the prevalence of BAV and of aortic dilatation amongst family members is uncertain.

Methods And Results: A systematic review and meta-analysis of original reports of screening for BAV.

Clinical support during COVID-19: An opportunity for service and learning? A cross-sectional survey of UK medical students.

Purpose: Medical students providing support to clinical teams during Covid-19 may have been an opportunity for service and learning. We aimed to understand why the reported educational impact has been mixed to inform future placements.

Methods: We conducted a cross-sectional survey of medical students at UK medical schools during the first Covid-19 'lockdown' period in the UK (March-July 2020).

An assessment of adherence to CARE reporting standards by case reports published in in 2018.

Background: Case reports are subject to significant variation in their content, and the absence of pertinent case details can limit their benefit to the medical community. To aid this, a reporting standard (CARE) has been developed. Case reports published in () are subject to specific checks by editors to confirm compliance with the CARE reporting standard.

Supersaturated proteins are enriched at synapses and underlie cell and tissue vulnerability in Alzheimer's disease.

Neurodegenerative disorders progress across the brain in characteristic spatio-temporal patterns. A better understanding of the factors underlying the specific cell and tissue vulnerability responsible for such patterns could help identify the molecular origins of these conditions. To investigate these factors, based on the observation that neurodegenerative disorders are closely associated with the presence of aberrant protein deposits, we made the hypothesis that the vulnerability of cells and tissues is associated to the overall levels of supersaturated proteins, which are those most metastable against aggregation.

A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology.

Excitatory neurons are preferentially impaired in early Alzheimer's disease but the pathways contributing to their relative vulnerability remain largely unknown. Here we report that pathological tau accumulation takes place predominantly in excitatory neurons compared to inhibitory neurons, not only in the entorhinal cortex, a brain region affected in early Alzheimer's disease, but also in areas affected later by the disease. By analyzing RNA transcripts from single-nucleus RNA datasets, we identified a specific tau homeostasis signature of genes differentially expressed in excitatory compared to inhibitory neurons.

A protein homeostasis signature in healthy brains recapitulates tissue vulnerability to Alzheimer's disease.

In Alzheimer's disease, aggregates of Aβ and tau in amyloid plaques and neurofibrillary tangles spread progressively across brain tissues following a characteristic pattern, implying a tissue-specific vulnerability to the disease. We report a transcriptional analysis of healthy brains and identify an expression signature that predicts-at ages well before the typical onset-the tissue-specific progression of the disease. We obtain this result by finding a quantitative correlation between the histopathological staging of the disease and the expression patterns of the proteins that coaggregate in amyloid plaques and neurofibrillary tangles, together with those of the protein homeostasis components that regulate Aβ and tau.

A transcriptional signature of Alzheimer's disease is associated with a metastable subproteome at risk for aggregation.

It is well-established that widespread transcriptional changes accompany the onset and progression of Alzheimer's disease. Because of the multifactorial nature of this neurodegenerative disorder and its complex relationship with aging, however, it remains unclear whether such changes are the result of nonspecific dysregulation and multisystem failure or instead are part of a coordinated response to cellular dysfunction. To address this problem in a systematic manner, we performed a meta-analysis of about 1,600 microarrays from human central nervous system tissues to identify transcriptional changes upon aging and as a result of Alzheimer's disease.