Dementia risk reduction between DOACs and VKAs in AF: A systematic review and meta-analysis.

Introduction: Direct oral anticoagulants (DOACs) become the recommended treatment over vitamin K antagonists (VKA) in patients with non-valvular atrial fibrillation (AF). However, their effectiveness in reducing cognitive impairment and dementia compared to VKA remains unclear.

Methods: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Database.

A 6-month, prospective, randomized controlled trial of customized adherence enhancement versus a bipolar-specific educational control in poorly adherent adolescents and young adults living with bipolar disorder.

Objective: Few studies have addressed medication adherence in adolescents and young adults (AYAs) with bipolar disorder (BD). This 6-month prospective randomized-controlled trial (RCT) tested customized adherence enhancement for adolescents and young adults (CAE-AYA), a behavioral intervention for AYAs versus enhanced treatment as usual (ETAU).

Methods: Inclusion criteria were AYAs age 13-21 with BD type I or II with suboptimal adherence defined as missing ≥20% of medications.

Tetrazine Amino Acid Encoding for Rapid and Complete Protein Bioconjugation.

Generating protein conjugates using the bioorthogonal ligation between tetrazines and -cyclooctene groups avoids the need to manipulate cysteine amino acids; this ligation is rapid, site-specific, and stoichiometric and allows for labeling of proteins in complex biological environments. Here, we provide a protocol for the expression of conjugation-ready proteins at high yields in with greater than 95% encoding and labeling fidelity. This protocol focuses on installing the Tet2 tetrazine amino acid using an optimized genetic code expansion (GCE) machinery system, Tet2 pAJE-E7, to direct Tet2 encoding at TAG stop codons in BL21 strains, enabling reproducible expression of Tet2-proteins that quantitatively react with trans-cyclooctene (TCO) groups within 5 min at room temperature and physiological pH.

Partial wrapping of single-stranded DNA by replication protein A and modulation through phosphorylation.

Single-stranded DNA (ssDNA) intermediates which emerge during DNA metabolic processes are shielded by replication protein A (RPA). RPA binds to ssDNA and acts as a gatekeeper to direct the ssDNA towards downstream DNA metabolic pathways with exceptional specificity. Understanding the mechanistic basis for such RPA-dependent functional specificity requires knowledge of the structural conformation of ssDNA when RPA-bound.

Phosphorylation Code of Human Nucleophosmin Includes Four Cryptic Sites for Hierarchical Binding of 14-3-3 Proteins.

Nucleophosmin (NPM1) is the 46th most abundant human protein with many functions whose dysregulation leads to various cancers. Pentameric NPM1 resides in the nucleolus but can also shuttle to the cytosol. NPM1 is regulated by multisite phosphorylation, yet molecular consequences of site-specific NPM1 phosphorylation remain elusive.