The Ni(II) precatalyst (C1) featuring the phosphonite ancillary ligand Phen-DalPhos (L1) was employed in the cross-coupling of (hetero)anilines with (hetero)aryl chlorides and in the diarylation of ammonia with (hetero)aryl chlorides to afford heteroatom-dense di(hetero)arylamines. The PAd2-DalPhos precatalyst C4 provided complementary reactivity in cross-couplings of indoles with (hetero)aryl chlorides. Taken together, the demonstration of room-temperature reactivity within each of the reaction classes examined and the observation of useful chemoselectivity at low loading (≤0.5 mol % Ni) and on gram-scale distinguishes C1 and C4 from other metal catalysts (i.e., copper, palladium, nickel, or other) within the field of C–N cross-coupling chemistry.
Background: Improving patient care and safety requires high-quality evidence. The objective of this study was to systematically review the existing evidence for patient safety (PS) and quality improvement initiatives in breast reconstruction. Methods: A systematic review of the published plastic surgery literature was undertaken using a computerized search and following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Publication descriptors, methodological details, and results were extracted. Articles were assessed for methodological quality and clinical heterogeneity. Descriptive statistics were completed, and a meta-analysis was considered. Results: Forty-six studies were included. Most studies were retrospective (52.2%) and from the third level of evidence (60.9%). Overall, the scientific quality was moderate, with randomized controlled trials generally being higher quality. Studies investigating approaches to reduce seroma (28.3% of included articles) suggested a potential benefit of quilting sutures. Studies focusing on infection (26.1%) demonstrated potential benefits to prophylactic antibiotics and drain use under 21 days. Enhanced recovery after surgery protocols (10.9%) overall did not compromise PS and was beneficial in reducing opioid use and length of stay. Interventions to increase flap survival (10.9%) demonstrated a potential benefit of nitroglycerin on mastectomy skin flaps. Conclusions: Overall, studies were of moderate quality and investigated several worthwhile interventions. More validated, standardized outcome measures are required, and studies focusing on interventions to reduce thromboembolic events and bleeding risk could further improve PS.
Memory formation and maintenance is a dynamic process involving the modulation of the actin cytoskeleton at synapses. Understanding the signaling pathways that contribute to actin modulation is important for our understanding of synapse formation and function, as well as learning and memory. Here, we focused on the importance of the actin regulator, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1), in hippocampal dependent behaviours and development. We report that male mice lacking NCK1 have impairments in both short-term and working memory, as well as spatial learning. Additionally, we report sex-differences in memory impairment showing that female mice deficient in NCK1 fail at reversal learning in a spatial learning task. We find that NCK1 is expressed in post-mitotic neurons but is dispensable for neuronal proliferation and migration in the developing hippocampus. Morphologically, NCK1 is not necessary for overall neuronal dendrite development. However, neurons lacking NCK1 have lower dendritic spine and synapse densitiesin vitroandin vivo. EM analysis reveal increased PSD thickness in the hippocampal CA1 region of NCK1 deficient mice. Mechanistically, we find the turnover of actin-filaments in dendritic spines is accelerated in neurons that lack NCK1. Together, these findings suggest that NCK1 contributes to hippocampal-dependent memory by stabilizing actin dynamics and dendritic spine formation.SIGNIFICANCE STATEMENT:Understanding the molecular signaling pathways that contribute to memory formation, maintenance, and elimination will lead to a better understanding of the genetic influences on cognition and cognitive disorders and will direct future therapeutics. Here, we report that the NCK1 adaptor protein modulates actin-filament turnover in hippocampal dendritic spines. Mice lacking NCK1 show sex-dependent deficits in hippocampal memory formation tasks, have altered postsynaptic densities, and reduced synaptic density. Together, our work implicates NCK1 in the regulation of actin cytoskeleton dynamics and normal synapse development which is essential for memory formation.
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