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BACKGROUND: Medicare-funded home healthcare (HHC) delivers skilled nursing, therapy, and related services through visits to the patients home. Nearly one-third (31%) of HHC patients have diagnosed dementia, but little is currently known regarding how HHC utilization and care delivery differ for persons living with dementia (PLwD). METHODS: We drew on linked 2012-2018 Health and Retirement Study and Medicare claims for a national cohort of 1 940 community-living older adults. We described differences in HHC admission, length of stay, and referral source by patient dementia status and used weighted, multivariable logistic and negative binomial models to estimate the relationship between dementia and HHC visit type and intensity while adjusting for sociodemographic characteristics, health and functional status, and geographic/community factors. RESULTS: PLwD had twice the odds of using HHC during a 2-year observation period, compared to those without dementia (odds ratio [OR]: 2.03; p < .001). They were more likely to be referred to HHC without a preceding hospitalization (49.4% vs 32.1%; p < .001) and incurred a greater number of HHC episodes (1.4 vs 1.0; p < .001) and a longer median HHC length of stay (55.8 days vs 40.0 days; p < .001). Among post-acute HHC patients, PLwD had twice the odds of receiving social work services (unadjusted odds ratio [aOR]: 2.15; p = .008) and 3 times the odds of receiving speech-language pathology services (aOR: 2.92; p = .002). CONCLUSIONS: Findings highlight HHCs importance as a care setting for community-living PLwD and indicate the need to identify care delivery patterns associated with positive outcomes for PLwD and design tailored HHC clinical pathways for this patient subpopulation.

OBJECTIVES: Home-based medical care (HBMC) delivers physician or advanced practice provider-led medical services for patients in private residences and domiciliary settings (eg, assisted living facilities, group/boarding homes). We aimed to examine the time trends in HBMC utilization by care settings. DESIGN: Analyses of HBMC utilization at the national and state levels during the years 2012-2019. SETTING AND PARTICIPANTS: With Medicare public use files, we calculated the state-level utilization rate of HBMC among fee-for-service (FFS) Medicare beneficiaries, measured by visits per 1000 FFS enrollees, in private residences and domiciliary settings, both separately and combined. METHODS: We assessed the trend of HBMC utilization over time via linear mixed models with random intercept for state, adjusting for the following state-level markers of HBMC supply and demand: number of HBMC providers, state ranking of total assisted living and residential care capacity, and the proportion of FFS beneficiaries with dementia, dual eligibility for Medicaid, receiving home health services, and Medicare Advantage. RESULTS: Total HBMC visits in the United States increased from 3,911,778 in 2012 to 5,524,939 in 2019. The median (interquartile range) state-level HBMC utilization rate per 1000 FFS population was 67.6 (34.1-151.3) visits overall, 17.3 (7.9-41.9) visits in private residences, and 47.7 (23.1-86.6) visits in domiciliary settings. The annual percentage increase of utilization rates was significant for all care settings in crude models (3%-8%), and remained significant for overall visits and visits in domiciliary settings (2%-4%), but not in private residences. CONCLUSIONS AND IMPLICATIONS: The national-level growth in HBMC from 2012-2019 was largely driven by a growth of HBMC occurring in domiciliary settings. To meet the needs of a growing aging population, future studies should focus efforts on policy and payment issues to address inequities in access to HBMC services for homebound older adults, and examine drivers of HBMC growth at regional and local levels.

Protein kinases control nearly every facet of cellular function. These key signaling nodes integrate diverse pathway inputs to regulate complex physiological processes, and aberrant kinase signaling is linked to numerous pathologies. While fluorescent protein-based biosensors have revolutionized the study of kinase signaling by allowing direct, spatiotemporally precise kinase activity measurements in living cells, powerful new molecular tools capable of robustly tracking kinase activity dynamics across diverse experimental contexts are needed to fully dissect the role of kinase signaling in physiology and disease. Here, we report the development of an ultrasensitive, second-generation excitation-ratiometric protein kinase A (PKA) activity reporter (ExRai-AKAR2), obtained via high-throughput linker library screening, that enables sensitive and rapid monitoring of live-cell PKA activity across multiple fluorescence detection modalities, including plate reading, cell sorting and one- or two-photon imaging. Notably, in vivo visual cortex imaging in awake mice reveals highly dynamic neuronal PKA activity rapidly recruited by forced locomotion.

Escherichia coli single-stranded DNA (ssDNA) binding protein (SSB) is the defining bacterial member of ssDNA binding proteins essential for DNA maintenance. SSB binds ssDNA with a variable footprint of ∼30-70 nucleotides, reflecting partial or full wrapping of ssDNA around a tetramer of SSB. We directly imaged single molecules of SSB-coated ssDNA using total internal reflection fluorescence (TIRF) microscopy and observed intramolecular condensation of nucleoprotein complexes exceeding expectations based on simple wrapping transitions. We further examined this unexpected property by single-molecule force spectroscopy using magnetic tweezers. In conditions favoring complete wrapping, SSB engages in long-range reversible intramolecular interactions resulting in condensation of the SSB-ssDNA complex. RecO and RecOR, which interact with SSB, further condensed the complex. Our data support the idea that RecOR--and possibly other SSB-interacting proteins-function(s) in part to alter long-range, macroscopic interactions between or throughout nucleoprotein complexes by microscopically altering wrapping and bridging distant sites.