Circulating extracellular vesicles (EVs) are a novel and emerging biomarker for nonalcoholic steatohepatitis (NASH). It has been demonstrated that total circulating EVs and hepatocyte‐derived EVs are elevated in male mice with diet‐induced NASH. How hepatocyte‐derived EVs change over time and other cellular sources of EVs in NASH have not been determined. Our objective was to define the quantitative evolution of hepatocyte‐derived, macrophage‐derived, neutrophil‐derived, and platelet‐derived EVs in male and female mice with dietary NASH. Fluorescently labeled antibodies and a nanoscale flow cytometer were used to detect plasma levels of EVs. Asialoglycoprotein receptor 1 (ASGR1) and cytochrome P450 family 2 subfamily E member 1 (CYP2E1) are markers of hepatocyte‐derived EVs; galectin 3 is a marker of macrophage‐derived EVs; common epitope on lymphocyte antigen 6 complex, locus G/C1 (Ly‐6G and Ly‐6C) is a marker of neutrophil‐derived EVs; and clusters of differentiation 61 (CD61) is a marker of platelet‐derived EVs. Nonalcoholic fatty liver disease activity score (NAS) was calculated using hematoxylin and eosin‐stained liver sections, and magnetic resonance imaging (MRI) was used for measurement of the fat fraction and elastography. Hepatocyte‐derived EVs increased in both male and female mice at 12 and 10 weeks of feeding, respectively, and remained elevated at 24 weeks in both male and female mice and at 48 weeks in male mice and 36 weeks in female mice. Macrophage‐ and neutrophil‐derived EVs were significantly elevated at 24 weeks of dietary feeding concomitant with the histologic presence of inflammatory foci in the liver. In fat‐, fructose‐, and cholesterol‐ (FFC) fed male mice, platelet‐derived EVs were elevated at 12, 24, and 48 weeks, whereas in female mice, platelet derived EVs were significantly elevated at 24 weeks. Hepatocyte‐, macrophage‐ and neutrophil‐derived EVs correlated well with the histologic NAS. Conclusion: Circulating cell‐type‐specific EVs may be a novel biomarker for NASH diagnosis and longitudinal follow up.

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Objective To investigate types and intensity of pain experienced by individuals with cerebral palsy (CP) and common pain-relieving approaches used by caregivers. Design The approach was cross-sectional, using standardized interviews. Setting Individuals with CP were recruited from a specialty health care hospital. Participants Eighty-six individuals (N=86; mean age, 17.2 years; male, 58%) with CP and complex communication needs participated. Interventions Not applicable. Main Outcome Measures Pain type, mean pain intensity (MPI) (graded on a scale of 0=no pain to 10=worst possible pain), and mean pain relief (MPR) (graded on a scale of 0=intervention did not help at all to 10=intervention completely relieved pain) were assessed by caregiver report as part of the Dalhousie Pain Interview for each type of pain experienced in the previous 7 days. Results Caregivers reported that 58 participants (67%) had experienced pain in the previous 7 days. MPI was 7.7±1.8 when the pain was worst in the previous 7 days. The 2 most common types of pain included musculoskeletal pain (n=70) and gastrointestinal pain (n=11). The most frequent treatment to relieve musculoskeletal pain was changing positions (n=27, MPI=5.1±2.3, MPR=6.6±2.1), medication (n=25, MPI=7.4±1.6, MPR=5.3±1.9), and massage (n=19, MPI=6.7±1.9, MPR=5.2±1.7). To treat gastrointestinal pain, medication was typically used (n=4, MPI=4.8±1.4, MPR=5.5±1.0), although no treatment was just as common (n=4, MPI=4.5±2.3). Conclusions The results indicate that musculoskeletal pain is prevalent in individuals with CP, and changing physical positions and providing medication are strategies most used by caregivers.

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Background: Having depression and living in a rural environment have separately been associated with poor diabetes outcomes, but there little is known about the interaction between the 2 risk factors. This study investigates the association of depression and rurality with glycemic control in adults, as well as their interaction. Methods: This is a repeated cross-sectional study with data collected from 2010 to 2017 (n = 1,697,173 patient-year observations), comprising a near-complete census of patients with diabetes in Minnesota. The outcome of interest was glycemic control defined as hemoglobin A1c under 8%. We used a logit model with clinic-level random effects to predict glycemic control as a function of depression, patient rurality, and their interaction, adjusted for differences in observed characteristics of the patient, clinic, and patient's neighborhood. Results: Having depression was associated with lower probability of achieving glycemic control (P < .001). Although rurality alone had no association with glycemic control, significant interactions existed between depression and rurality. Living in a small rural town mitigated the negative association between depression and glycemic control (P < .001). Conclusion: Although patients with depression had poorer glycemic control, living in a small rural town reduced the negative association between depression and glycemic control. (J Am Board Fam Med 2020;33:913-922.