Persistent Fibroadipogenic Progenitor Expansion Following Transient DUX4 Expression Provokes a Profibrotic State in a Mouse Model for FSHD.

FSHD is caused by loss of silencing of the DUX4 gene, but the DUX4 protein has not yet been directly detected immunohistologically in affected muscle, raising the possibility that DUX4 expression may occur at time points prior to obtaining adult biopsies for analysis, with consequent perturbations of muscle being responsible for disease progression. To test the extent to which muscle can regenerate following DUX4-mediated degeneration, we employed an animal model with reversible DUX4 expression, the iDUX4pA;HSA mouse. We find that muscle histology does recover substantially after DUX4 expression is switched off, with the extent of recovery correlating inversely with the duration of prior DUX4 expression. However, despite fairly normal muscle histology, and recovery of most cytological parameters, the fibroadipogenic progenitor compartment, which is significantly elevated during bouts of fiber-specific DUX4 expression, does not return to basal levels, even many weeks after a single burst of DUX4 expression. We find that muscle that has recovered from a DUX4 burst acquires a propensity for severe fibrosis, which can be revealed by subsequent cardiotoxin injuries. These results suggest that a past history of DUX4 expression leads to maintained pro-fibrotic alterations in the cellular physiology of muscle, with potential implications for therapeutic approaches.

Impact of River Channel Lateral Migration on Microbial Communities across a Discontinuous Permafrost Floodplain.

Permafrost soils store approximately twice the amount of carbon currently present in Earth's atmosphere and are acutely impacted by climate change due to the polar amplification of increasing global temperature. Many organic-rich permafrost sediments are located on large river floodplains, where river channel migration periodically erodes and redeposits the upper tens of meters of sediment. Channel migration exerts a first-order control on the geographic distribution of permafrost and floodplain stratigraphy and thus may affect microbial habitats. To examine how river channel migration in discontinuous permafrost environments affects microbial community composition, we used amplicon sequencing of the 16S rRNA gene on sediment samples from floodplain cores and exposed riverbanks along the Koyukuk River, a large tributary of the Yukon River in west-central Alaska. Microbial communities are sensitive to permafrost thaw: communities found in deep samples thawed by the river closely resembled near-surface active-layer communities in nonmetric multidimensional scaling analyses but did not resemble floodplain permafrost communities at the same depth. Microbial communities also displayed lower diversity and evenness in permafrost than in both the active layer and permafrost-free point bars recently deposited by river channel migration. Taxonomic assignments based on 16S and quantitative PCR for the methyl coenzyme M reductase functional gene demonstrated that methanogens and methanotrophs are abundant in older permafrost-bearing deposits but not in younger, nonpermafrost point bar deposits. The results suggested that river migration, which regulates the distribution of permafrost, also modulates the distribution of microbes potentially capable of producing and consuming methane on the Koyukuk River floodplain. IMPORTANCE Arctic lowlands contain large quantities of soil organic carbon that is currently sequestered in permafrost. With rising temperatures, permafrost thaw may allow this carbon to be consumed by microbial communities and released to the atmosphere as carbon dioxide or methane. We used gene sequencing to determine the microbial communities present in the floodplain of a river running through discontinuous permafrost. We found that the river's lateral movement across its floodplain influences the occurrence of certain microbial communities-in particular, methane-cycling microbes were present on the older, permafrost-bearing eroding riverbank but absent on the newly deposited river bars. Riverbank sediment had microbial communities more similar to those of the floodplain active-layer samples than permafrost samples from the same depth. Therefore, spatial patterns of river migration influence the distribution of microbial taxa relevant to the warming Arctic climate.

Factors associated with low-acuity hospital admissions in a public safety-net setting: a cross-sectional study.

BACKGROUND: Given system-level focus on avoidance of unnecessary hospitalizations, better understanding admission decision-making is of utility. Our study sought to identify factors associated with hospital admission versus discharge from the Emergency Department (ED) for a population of patients who were assessed as having low medical acuity at time of decision. METHODS: Using an institutional database, we identified ED admission requests received from March 1, 2018 to Feb 28, 2019 that were assessed by a physician at the time of request as potentially inappropriate based on lack of medical acuity. Focused chart review was performed to extract data related to patient demographics, socioeconomic information, measures of illness, and system-level factors such as previous healthcare utilization and day/time of presentation. A binary logistic regression model was constructed to correlate patient and system factors with disposition outcome of admission to the hospital versus discharge from the ED. Physician-reported contributors to admission decision-making and chief complaint/reason for admission were summarized. RESULTS: A total of 349 (77.2%) of 452 calls resulted in admission to the hospital and 103 (22.8%) resulted in discharge from the ED. Predictors of admission included age over 65 (OR 3.5 [95%CI 1.1-11.6], p = 0.039), homelessness (OR 3.3 [95% CI 1.7-6.4], p=0.001), and night/weekend presentation (OR 2.0 [95%CI 1.1-3.5], p = 0.020). The most common contributing factors to the decision to admit reported by the responding physician included: lack of outpatient social support (35.8% of admissions), homelessness (33.0% of admissions), and substance use disorder (23.5% of admissions). CONCLUSIONS: Physician medical decision-making regarding the need for hospitalization incorporates consideration of individual patient characteristics, social setting, and system-level barriers. Interventions aimed at reducing unnecessary hospitalizations, especially those involving patients with low medical acuity, should focus on underlying unmet needs and involve a broad set of perspectives.