The prevalence rates and correlates of mental or physical disability among recently resettled refugees, who undergo strenuous journeys before arriving in the US, remain unknown, masking potential health disparities. Self-reported disability was measured by the 2018 Annual Survey of Refugees (ASR), and defined as having a physical, mental, or other health condition for more than 6 months that precluded one from working. Prevalence rates of self-reported disability and sample correlates were investigated using descriptive and logistic regression analyses. Of N = 4259 participating refugees in ASR (Mean Age = 28.2, SD = 17.2; 52.5% male), 2875 responded to the disability question and 21.4% reported disability. About 33.7% were born in the Middle East region, 29.5% had no formal education, and 35% had an income of less than $15,000. Age (OR = 1.06, 95% Confidence Interval (CI) [1.06,1.07], p < 0.001), region of birth (OR = 1.82, 95% CI [1.31, 2.51], p < 0.001), employment status (OR = 3.31, 95% CI [2.67, 4.11], p < 0.001), and receiving food stamps (OR = 2.09, 95% CI [1.66, 2.62], p < 0.001) were associated with self-reported disability. Disability levels among refugees recently resettled in the United States are comparable to national disability rates in the US. Our results suggest that multiple aspects of the refugee experience (i.e., demographics, socioeconomic status, contextual migration history) need to be considered to understand the risk for health outcomes. Future investigations of disabilities in diverse refugee populations over time and tailored public health interventions to mitigate potential risk factors are warranted to promote health equity.

Accumulating evidence indicates that obesity with its associated metabolic dysregulation, including hyperinsulinemia and aberrant circadian rhythms, increases the risk for a variety of cancers including postmenopausal breast cancer. Caloric restriction can ameliorate the harmful metabolic effects of obesity and inhibit cancer progression but is difficult to implement and maintain outside of the clinic. In this study, we aim to test a time-restricted feeding (TRF) approach on mouse models of obesity-driven postmenopausal breast cancer. We show that TRF abrogates the obesity-enhanced mammary tumor growth in two orthotopic models in the absence of calorie restriction or weight loss. TRF also reduces breast cancer metastasis to the lung. Furthermore, TRF delays tumor initiation in a transgenic model of mammary tumorigenesis prior to the onset of obesity. Notably, TRF increases whole-body insulin sensitivity, reduces hyperinsulinemia, restores diurnal gene expression rhythms in the tumor, and attenuates tumor growth and insulin signaling. Importantly, inhibition of insulin secretion with diazoxide mimics TRF whereas artificial elevation of insulin through insulin pumps implantation reverses the effect of TRF, suggesting that TRF acts through modulating hyperinsulinemia. Our data suggest that TRF is likely to be effective in breast cancer prevention and therapy.

Serine rich splicing factor 3 (SRSF3) plays a critical role in liver function and its loss promotes chronic liver damage and regeneration. As a consequence, genetic deletion of SRSF3 in hepatocytes caused progressive liver disease and ultimately led to hepatocellular carcinoma. Here we show that SRSF3 is decreased in human liver samples with non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or cirrhosis that was associated with alterations in RNA splicing of known SRSF3 target genes. Hepatic SRSF3 expression was similarly decreased and RNA splicing dysregulated in mouse models of NAFLD and NASH. We showed that palmitic acid-induced oxidative stress caused conjugation of the ubiquitin like NEDD8 protein to SRSF3 and proteasome mediated degradation. SRSF3 was selectively neddylated at lysine11 and mutation of this residue (SRSF3-K11R) was sufficient to prevent both SRSF3 degradation and alterations in RNA splicing. Finally prevention of SRSF3 degradation in vivo partially protected mice from hepatic steatosis, fibrosis and inflammation. These results highlight a neddylation-dependent mechanism regulating gene expression in the liver that is disrupted in early metabolic liver disease and may contribute to the progression to NASH, cirrhosis and ultimately hepatocellular carcinoma.