Vital Directions For Health And Health Care: Priorities For 2025.

In 2016, ahead of the US presidential election, the National Academy of Medicine launched the strategic initiative Vital Directions for Health and Health Care-a series of papers on critical areas of US health care written by the nation's experts and intended to provide nonpartisan guidance to the incoming administration. The National Academy of Medicine continued the initiative in 2021. The current series, titled Vital Directions for Health and Health Care: Priorities for 2025, contains six articles on priority areas in US health and medicine that demand urgent attention.

Cell type transcriptional identities are maintained in cultured human brain tissue.

It is becoming more broadly accepted that human-based models are needed to better understand the complexities of the human nervous system and its diseases. The recently developed human brain organotypic culture model is one highly promising model that requires the involvement of neurosurgeons and neurosurgical patients. Studies have investigated the electrophysiological properties of neurons in such human tissues, but the maintenance of other cell types within explanted brain remains largely unknown.

Red Blood Cells Capture and Deliver Bacterial DNA to Drive Host Responses During Polymicrobial Sepsis.

Red blood cells (RBCs), traditionally recognized for their role in transporting oxygen, play a pivotal role in the body's immune response by expressing TLR9 and scavenging excess host cell-free DNA. DNA capture by RBCs leads to accelerated RBC clearance and triggers inflammation. Whether RBCs can also acquire microbial DNA during infections is unknown.

Common AAV gene therapy vectors show indiscriminate transduction of living human brain cell types.

The development of cell-type-specific gene therapy vectors for treating neurological diseases holds great promise, but has relied on animal models with limited translational utility. We have adapted an organotypic model to evaluate adeno-associated virus (AAV) transduction properties in living slices of human brain tissue. Using fluorescent reporter expression and single-nucleus RNA sequencing, we found that common AAV vectors show broad transduction of normal cell types, with protein expression most apparent in astrocytes; this work introduces a pipeline for identifying and optimizing AAV gene therapy vectors in human brain samples.