RESUMO
Maintaining body temperature is calorically expensive for endothermic animals1. Mammals eat more in the cold to compensate for energy expenditure2, but the neural mechanism underlying this coupling is not well understood. Through behavioural and metabolic analyses, we found that mice dynamically switch between energy-conservation and food-seeking states in the cold, the latter of which are primarily driven by energy expenditure rather than the sensation of cold. To identify the neural mechanisms underlying cold-induced food seeking, we used whole-brain c-Fos mapping and found that the xiphoid (Xi), a small nucleus in the midline thalamus, was selectively activated by prolonged cold associated with elevated energy expenditure but not with acute cold exposure. In vivo calcium imaging showed that Xi activity correlates with food-seeking episodes under cold conditions. Using activity-dependent viral strategies, we found that optogenetic and chemogenetic stimulation of cold-activated Xi neurons selectively recapitulated food seeking under cold conditions whereas their inhibition suppressed it. Mechanistically, Xi encodes a context-dependent valence switch that promotes food-seeking behaviours under cold but not warm conditions. Furthermore, these behaviours are mediated by a Xi-to-nucleus accumbens projection. Our results establish Xi as a key region in the control of cold-induced feeding, which is an important mechanism in the maintenance of energy homeostasis in endothermic animals.
Assuntos
Temperatura Corporal , Temperatura Baixa , Comportamento Alimentar , Tálamo , Animais , Camundongos , Temperatura Corporal/fisiologia , Mapeamento Encefálico , Cálcio/metabolismo , Comportamento Alimentar/fisiologia , Metabolismo Energético/fisiologia , Tálamo/anatomia & histologia , Tálamo/citologia , Tálamo/fisiologia , Optogenética , Neurônios/metabolismo , Núcleo Accumbens/citologia , Núcleo Accumbens/fisiologia , Homeostase/fisiologia , Termogênese/fisiologiaRESUMO
BACKGROUND: Administrative claims in total joint arthroplasty are used for observational studies and payment adjustments under the Comprehensive Care for Joint Replacement (CJR) legislation. Claims data have not been validated against prospective surgical outcome registries for primary total hip (THA) or knee arthroplasty (TKA). We hypothesized that significant differences in reported comorbidity and adverse event measures exist between administrative claims and prospective registry data relevant to payment adjudication under the CJR reimbursement model. METHODS: Comorbidities and outcomes in primary TKA and THA in the United Healthcare and Medicare Standard Analytical File 5% Sample insurance claims datasets (PearlDiver Technologies, Inc) were compared to age-matched cohorts from the National Surgical Quality Improvement Program (ACS-NSQIP) surgical outcomes data from 2007 to 2011 using comparable International Classification of Diseases, Ninth Revision, Clinical Modification and Current Procedural Terminology codes at 30, 90, and 360 days from index arthroplasty. Pearson's chi-square test was used for statistical analyses. RESULTS: The total study population included 93,953 primary THA and 176,944 TKA patients. Primary TKA and THA patients in insurance claims cohorts had significantly fewer reported comorbidities, higher rates of surgical site infection, pulmonary embolism, wound dehiscence, thromboembolic events, and neurologic deficits, and lower reported rates of revision surgery than ACS-NSQIP cohorts within 30 days of primary TKA and THA. Cumulative incidence of adverse events increased significantly from 30 to 360 days after primary arthroplasty. CONCLUSION: We report significant discordance in the prevalence of patient comorbidities and incidence of adverse events in primary THA and TKA between ACS-NSQIP and the administrative claims data of Medicare and United Healthcare. These disparities have implications for observational outcome studies as well as payment adjudication under the CJR reimbursement model in total joint arthroplasty.