Relation of addiction genes to hypothalamic gene changes subserving genesis and gratification of a classic instinct, sodium appetite.

Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked adrenocorticotropic hormone (ACTH), and reproduction. Genome-wide microarrays in sodium-deficient mice or after ACTH infusion showed up-regulation of hypothalamic genes, including dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP-32), dopamine receptors-1 and -2, α-2C- adrenoceptor, and striatally enriched protein tyrosine phosphatase (STEP). Both DARPP-32 and neural plasticity regulator activity-regulated cytoskeleton associated protein (ARC) were up-regulated in lateral hypothalamic orexinergic neurons by sodium deficiency. Administration of dopamine D1 (SCH23390) and D2 receptor (raclopride) antagonists reduced gratification of sodium appetite triggered by sodium deficiency. SCH23390 was specific, having no effect on osmotic-induced water drinking, whereas raclopride also reduced water intake. D1 receptor KO mice had normal sodium appetite, indicating compensatory regulation. Appetite was insensitive to SCH23390, confirming the absence of off-target effects. Bilateral microinjection of SCH23390 (100 nM in 200 nL) into rats' lateral hypothalamus greatly reduced sodium appetite. Gene set enrichment analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates and cocaine). This finding of concerted gene regulation was attenuated on gratification with perplexingly rapid kinetics of only 10 min, anteceding significant absorption of salt from the gut. Salt appetite and hedonic liking of salt taste have evolved over >100 million y (e.g., being present in Metatheria). Drugs causing pleasure and addiction are comparatively recent and likely reflect usurping of evolutionary ancient systems with high survival value by the gratification of contemporary hedonic indulgences. Our findings outline a molecular logic for instinctive behavior encoded by the brain with possible important translational-medical implications.

Voices from the Pandemic: A Qualitative Study of Family Experiences and Suggestions regarding the Care of Critically Ill Patients.

Rationale: Intensive care unit (ICU) visitation restrictions during the coronavirus disease (COVID-19) pandemic have drastically reduced family-engaged care. Understanding the impact of physical distancing on family members of ICU patients is needed to inform future policies. Objectives: To understand the experiences of family members of critically ill patients with COVID-19 when physically distanced from their loved ones and to explore ways clinicians may support them. Methods: This qualitative study of an observational cohort study reports data from 74 family members of ICU patients with COVID-19 at 10 United States hospitals in four states, chosen based on geographic and demographic diversity. Adult family members of patients admitted to the ICU with COVID-19 during the early phase of the pandemic (February-June 2020) were invited to participate in a phone interview. Interviews followed a semistructured guide to assess four constructs: illness narrative, stress experiences, communication experiences, and satisfaction with care. Interviews were transcribed verbatim and analyzed using an inductive approach to thematic analysis. Results: Among 74 interviewees, the mean age was 53.0 years, 55% were white, and 76% were female. Physical distancing contributed to substantial stress and harms (nine themes). Participants described profound suffering and psychological illness, unfavorable perceptions of care, and weakened therapeutic relationship between family members and clinicians. Three communication principles emerged as those most valued by family members: contact, consistency, and compassion (the 3Cs). Family members offered suggestions to guide clinicians faced with communicating with physically distanced families. Conclusions: Visitation restrictions impose substantial psychological harms upon family members of critically ill patients. Derived from the voics of family members, our findings warrant strong consideration when implementing visitation restrictions in the ICU and advocate for investment in infrastructure (including staffing and videoconferencing) to support communication. This study offers family-derived recommendations to operationalize the 3Cs to guide and improve communication in times of physical distancing during the COVID-19 pandemic and beyond.