Structural determinants of the interactions of catechins with Aß oligomers and lipid membranes.

The aberrant self-assembly of intrinsically disordered proteins (IDPs) into soluble oligomers and their interactions with biological membranes underlie the pathogenesis of numerous neurodegenerative diseases, including Alzheimer's disease. Catechins have emerged as useful tools to reduce the toxicity of IDP oligomers by modulating their interactions with membranes. However, the structural determinants of catechin binding to IDP oligomers and membranes remain largely elusive. Here, we assemble a catechin library by combining several naturally occurring chemical modifications and, using a coupled NMR-statistical approach, we map at atomic resolution the interactions of such library with the Alzheimer's-associated amyloid-beta (Aß) oligomers and model membranes. Our results reveal multiple catechin affinity drivers and show that the combination of affinity-reducing covalent changes may lead to unexpected net gains in affinity. Interestingly, we find that the positive cooperativity is more prevalent for Aß oligomers than membrane binding, and that the determinants underlying catechin recognition by membranes are markedly different from those dissected for Aß oligomers. Notably, we find that the unanticipated positive cooperativity arises from the critical regulatory role of the gallate catechin moiety, which recruits previously disengaged substituents into the binding interface and leads to an overall greater compaction of the receptor-bound conformation. Overall, the previously elusive structural attributes mapped here provide an unprecedented foundation to establish structure-activity relationships of catechins.

The Tangible Benefits of Living Donation: Results of a Qualitative Study of Living Kidney Donors.

The framework currently used for living kidney donor selection is based on estimation of acceptable donor risk, under the premise that benefits are only experienced by the recipient. However, some interdependent donors might experience tangible benefits from donation that cannot be considered in the current framework (ie, benefits experienced directly by the donor that improve their daily life, well-being, or livelihood). METHODS: We conducted semistructured interviews with 56 living kidney donors regarding benefits experienced from donation. Using a qualitative descriptive and constant comparative approach, themes were derived inductively from interview transcripts by 2 independent coders; differences in coding were reconciled by consensus. RESULTS: Of 56 participants, 30 were in interdependent relationships with their recipients (shared household and/or significant caregiving responsibilities). Tangible benefits identified by participants fell into 3 major categories: health and wellness benefits, time and financial benefits, and interpersonal benefits. Participants described motivations to donate a kidney based on a more nuanced understanding of the benefits of donation than accounted for by the current "acceptable risk" paradigm. DISCUSSION: Tangible benefits for interdependent donors may shift the "acceptable risk" paradigm (where no benefit is assumed) of kidney donor evaluation to a risk/benefit paradigm more consistent with other surgical decision-making.

Kidney Dyads: Caregiver Burden and Relationship Strain Among Partners of Dialysis and Transplant Patients.

BACKGROUND: Caring for dialysis patients is difficult, and this burden often falls on a spouse or cohabiting partner (henceforth referred to as caregiver-partners). At the same time, these caregiver-partners often come forward as potential living kidney donors for their loved ones who are on dialysis (henceforth referred to as patient-partners). Caregiver-partners may experience tangible benefits to their well-being when their patient-partner undergoes transplantation, yet this is seldom formally considered when evaluating caregiver-partners as potential donors. METHODS: To quantify these potential benefits, we surveyed caregiver-partners of dialysis patients and kidney transplant (KT) recipients (N = 99) at KT evaluation or post-KT. Using validated tools, we assessed relationship satisfaction and caregiver burden before or after their patient-partner's dialysis initiation and before or after their patient-partner's KT. RESULTS: Caregiver-partners reported increases in specific measures of caregiver burden (P = 0.03) and stress (P = 0.01) and decreases in social life (P = 0.02) and sexual relations (P < 0.01) after their patient-partner initiated dialysis. However, after their patient-partner underwent KT, caregiver-partners reported improvements in specific measures of caregiver burden (P = 0.03), personal time (P < 0.01), social life (P = 0.01), stress (P = 0.02), sexual relations (P < 0.01), and overall quality of life (P = 0.03). These improvements were of sufficient impact that caregiver-partners reported similar levels of caregiver burden after their patient-partner's KT as before their patient-partner initiated dialysis (P = 0.3). CONCLUSIONS: These benefits in caregiver burden and relationship quality support special consideration for spouses and partners in risk-assessment of potential kidney donors, particularly those with risk profiles slightly exceeding center thresholds.