Associative learning contributes to the persistence of fatigue-like behavior in male mice in a model of cancer survivorship.

Persistent fatigue is a debilitating side effect that impacts a significant proportion of cancer survivors for which there is not yet an FDA-approved treatment. While certainly a multi-factorial problem, persistent fatigue could be due, in part, to associations learned during treatment. Therefore, we sought to investigate the role of associative learning in the persistence of fatigue using a preclinical model of cancer survivorship. For this purpose, we used a murine model of human papilloma virus-related head and neck cancer paired with a curative regimen of cisplatin-based chemoradiation in male C57BL/6J mice. Fatigue-like behavior was assessed by measuring variations in voluntary wheel running using a longitudinal design. Treatment robustly decreased voluntary wheel running, and this effect persisted for more than a month posttreatment. However, when wheels were removed during treatment, to minimize treatment-related fatigue, mice showed a more rapid return to baseline running levels. We confirmed that the delayed recovery observed in mice with continual wheel access was not due to increased treatment-related toxicity, in fact running attenuated cisplatin-induced kidney toxicity. Finally, we demonstrated that re-exposure to a treatment-related olfactory cue acutely re-instated fatigue. These data provide the first demonstration that associative processes can modulate the persistence of cancer-related fatigue-like behavior.

SARS-CoV-2 Variants in Rhode Island.

COVID-19 is a worldwide public health emergency caused by SARS-CoV-2. Genomic surveillance of SARS-CoV-2 emerging variants is important for pandemic monitoring and informing public health responses. Through an interstate academic-public health partnership, we established Rhode Island's capacity to sequence SARS-CoV-2 genomes and created a systematic surveillance program to monitor the prevalence of SARS-CoV-2 variants in the state. We describe circulating SARS-CoV-2 lineages in Rhode Island; provide a timeline for the emerging and expanding contribution of variants of concern (VOC) and variants of interest (VOI), from their first introduction to their eventual predominance over other lineages; and outline the frequent identification of known adaptively beneficial spike protein mutations that appear to have independently arisen in non-VOC/non-VOI lineages. Overall, the described Rhode Island- centric genomic surveillance initiative provides a valuable perspective on SARS-CoV-2 in the state and contributes data of interest for future epidemiological studies and state-to-state comparisons.