Changes in skeletal troponin C (sTnC) structure during thin filament activation by Ca2+ and strongly bound cross-bridge states were monitored by measuring the linear dichroism of the 5' isomer of iodoacetamidotetramethylrhodamine (5'IATR), attached to Cys98 (sTnC-5'ATR), in sTnC-5'ATR reconstituted single skinned fibers from rabbit psoas muscle. To isolate the effects of Ca2+ and cross-bridge binding on sTnC structure, maximum Ca2+-activated force was inhibited with 0.5 mM AlF4- or with 30 mM 2,3 butanedione-monoxime (BDM) during measurements of the Ca2+ dependence of force and dichroism. Dichroism was 0.08 +/- 0.01 (+/- SEM, n = 9) in relaxing solution (pCa 9.2) and decreased to 0.004 +/- 0.002 (+/- SEM, n = 9) at pCa 4.0. Force and dichroism had similar Ca2+ sensitivities. Force inhibition with BDM caused no change in the amplitude and Ca2+ sensitivity of dichroism. Similarly, inhibition of force at pCa 4.0 with 0.5 mM AlF4- decreased force to 0.04 +/- 0.01 of maximum (+/- SEM, n = 3), and dichroism was 0.04 +/- 0.03 (+/- SEM, n = 3) of the value at pCa 9.2 and unchanged relative to the corresponding normalized value at pCa 4.0 (0.11 +/- 0.05, +/- SEM; n = 3). Inhibition of force with AlF4- also had no effect when sTnC structure was monitored by labeling with either 5-dimethylamino-1-napthalenylsulfonylaziridine (DANZ) or 4-(N-(iodoacetoxy)ethyl-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole (NBD). Increasing sarcomere length from 2.5 to 3.6 microm caused force (pCa 4.0) to decrease, but had no effect on dichroism. In contrast, rigor cross-bridge attachment caused dichroism at pCa 9.2 to decrease to 0.56 +/- 0.03 (+/- SEM, n = 5) of the value at pCa 9. 2, and force was 0.51 +/- 0.04 (+/- SEM, n = 6) of pCa 4.0 control. At pCa 4.0 in rigor, dichroism decreased further to 0.19 +/- 0.03 (+/- SEM, n = 6), slightly above the pCa 4.0 control level; force was 0.66 +/- 0.04 of pCa 4.0 control. These results indicate that cross-bridge binding in the rigor state alters sTnC structure, whereas cycling cross-bridges have little influence at either submaximum or maximum activating [Ca2+].

Objectives To examine the circumstances and needs of older adults who were “kinless,” defined as having no living spouse or children, when they developed dementia. Methods We conducted a secondary analysis of information from the Adult Changes in Thought (ACT) Study. Among 848 participants diagnosed with dementia between 1992 and 2016, we identified 64 who had no living spouse or child at dementia onset. We then conducted a qualitative analysis of administrative documents pertaining to these participants: handwritten comments recorded after each study visit, and medical history documents containing clinical chart notes from participants’ medical records. Results In this community dwelling cohort of older adults diagnosed with dementia, 8.4% were kinless at dementia onset. Participants in this sample had an average age of 87 years old, half lived alone, and one-third lived with unrelated persons. Through inductive content analysis we identified four themes that describe their circumstances and needs: 1) life trajectories, 2) caregiving resources, 3) care needs and gaps, and 4) turning points in caregiving arrangements. Discussion Our qualitative analysis reveals that the life trajectories that led members of the analytic cohort to be kinless at dementia onset were quite varied. This research highlights the importance of non-family caregivers, and participants’ own roles as caregivers. Our findings suggest that providers and health systems may need to work with other parties to directly provide dementia caregiving support rather than rely on family, and address factors such as neighborhood affordability that particularly affect older adults who have limited family support.

In late summer of 2020, we interviewed 45 senior leaders of social services and health care organizations serving older adults throughout Washington State about service demand, new challenges, and organizational adaptations. These organizations work with people made particularly vulnerable in the pandemic. A significant share reported that half or more of their clients live at or below the poverty line (54%), are people of color (29%), or have limited English language proficiency (20%). The state’s aging network leveraged strong partnerships, expertise, and community knowledge to provide trusted essential services to older Washingtonians and their caregivers. The role of trust as an enabler of emergency response and connection in the context of gentrification, the digital divide, employment loss, and language service gaps will be discussed, as will lack of trust as a barrier to service access, particularly for Latinx immigrant and migrant older adults.

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