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1.
Alzheimers Dement ; 20(5): 3629-3648, 2024 05.
Article in English | MEDLINE | ID: mdl-38556850

ABSTRACT

Alzheimer's disease (AD) is a growing problem worldwide. Since ABCA7's identification as a risk gene, it has been extensively researched for its role in the disease. We review its recently characterized structure and what the mechanistic insights teach us about its function. We furthermore provide an overview of identified ABCA7 mutations, their presence in different ancestries and protein domains and how they might cause AD. For ABCA7 PTC variants and a VNTR expansion, haploinsufficiency is proposed as the most likely mode-of-action, although splice events could further influence disease risk. Overall, the need to better understand expression of canonical ABCA7 and its isoforms in disease is indicated. Finally, ABCA7's potential functions in lipid metabolism, phagocytosis, amyloid deposition, and the interplay between these three, is described. To conclude, in this review, we provide a comprehensive overview and discussion about the current knowledge on ABCA7 in AD, and what research questions remain. HIGHLIGHTS: Alzheimer's risk-increasing variants in ABCA7 can be found in up to 7% of AD patients. We review the recently characterized protein structure of ABCA7. We present latest insights in genetics, expression patterns, and functions of ABCA7.


Subject(s)
ATP-Binding Cassette Transporters , Alzheimer Disease , Humans , Alzheimer Disease/genetics , ATP-Binding Cassette Transporters/genetics , Genetic Predisposition to Disease , Mutation , Animals
2.
Appl Ergon ; 78: 251-262, 2019 Jul.
Article in English | MEDLINE | ID: mdl-29525267

ABSTRACT

Communication breakdowns in the operating room (OR) have been linked to errors during surgery. Robot-assisted surgery (RAS), a new surgical technology, can lead to new challenges in communication owing to the remote location of the surgeon away from the patient and bedside assistants. Nevertheless, few studies have studied communication strategies during RAS. In this study, 11 robot-assisted radical prostatectomies were recorded and the interaction events between the surgeon and two bedside surgical team members were categorized by modality (verbal/nonverbal), topic, and pair (sender and receiver). Both verbal and nonverbal modalities were used by all pairs. The percentage of nonverbal interactions differed significantly by pair: 66% for the Surgeon-Physician Assistant, 50% for the Physician Assistant-Scrub Nurse, and 25% for the Surgeon-Scrub Nurse, indicating different communication strategies across pairs. In addition, there was a significant dependence between topic and the percentages of verbal and nonverbal events for all pairs. Strategies to improve team communication during RAS should take into account the use of verbal and nonverbal communication means and the variation in interaction strategies based on the topic of communication.


Subject(s)
Gestures , Patient Care Team , Robotic Surgical Procedures , Humans , Nurses , Operating Rooms , Physician Assistants , Professional Role , Prostatectomy/methods , Speech , Surgeons
3.
Nat Commun ; 9(1): 2066, 2018 05 25.
Article in English | MEDLINE | ID: mdl-29802256

ABSTRACT

Fibrosis is a severe health problem characterized by progressive stiffening of tissues which causes organ malfunction and failure. A major bottleneck in developing new anti-fibrosis therapies is the lack of in vitro models that recapitulate dynamic changes in tissue mechanics during fibrogenesis. Here we create membranous human lung microtissues to model key biomechanical events occurred during lung fibrogenesis including progressive stiffening and contraction of alveolar tissue, decline in alveolar tissue compliance and traction force-induced bronchial dilation. With these capabilities, we provide proof of principle for using this fibrotic tissue array for multi-parameter, phenotypic analysis of the therapeutic efficacy of two anti-fibrosis drugs recently approved by the FDA. Preventative treatments with Pirfenidone and Nintedanib reduce tissue contractility and prevent tissue stiffening and decline in tissue compliance. In a therapeutic treatment regimen, both drugs restore tissue compliance. These results highlight the pathophysiologically relevant modeling capability of our novel fibrotic microtissue system.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Drug Evaluation, Preclinical/methods , Lung/drug effects , Pulmonary Fibrosis/drug therapy , Tissue Culture Techniques/methods , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cells, Cultured , Fibroblasts , Fibrosis , Humans , Indoles/pharmacology , Indoles/therapeutic use , Lung/pathology , Lung Compliance/drug effects , Primary Cell Culture , Pulmonary Fibrosis/pathology , Pyridones/pharmacology , Pyridones/therapeutic use , Tissue Scaffolds , Treatment Outcome
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