Scientific reports
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Observational Study
Validation of the Sleep Regularity Index in Older Adults and Associations with Cardiometabolic Risk.
Sleep disturbances, including insufficient sleep duration and circadian misalignment, confer risk for cardiometabolic disease. Less is known about the association between the regularity of sleep/wake schedules and cardiometabolic risk. This study evaluated the external validity of a new metric, the Sleep Regularity Index (SRI), among older adults (n = 1978; mean age 68.7 ± 9.2), as well as relationships between the SRI and cardiometabolic risk using data from the Multi-Ethnic Study of Atherosclerosis (MESA). ⋯ These results suggest that the SRI is a useful measure of sleep regularity in older adults. Additionally, sleep irregularity may represent a target for early identification and prevention of cardiometabolic disease. Future studies may clarify the causal direction of these effects, mechanisms underlying links between sleep irregularity and cardiometabolic risk, and the utility of sleep interventions in reducing cardiometabolic risk.
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Commensal microbiota induces colonic barrier structure and functions that contribute to homeostasis.
The intestinal barrier encompasses structural, permeability and immune aspects of the gut mucosa that, when disrupted, may contribute to chronic inflammation. Although gnotobiotic studies have demonstrated the effects of microbiota on mucosal and systemic immunity, as well as intestinal barrier architecture and innate immune characteristics, its impact on barrier function remains unclear. We compared germ-free and conventional mice, as well as mice colonized with human fecal microbiota that were followed for 21 days post-colonization. ⋯ Permeability to paracellular probes and mucus layer structure resembled that of conventional mice by day 7 post-colonization, coinciding with reduced claudin-1 expression and transient IL-18 production by intestinal epithelial cells. These post-colonization adaptations were associated with decreased systemic bacterial antigen exposure and reduced susceptibility to intestinal injury. In conclusion, commensal colonization promotes physiological barrier structural and functional adaptations that contribute to intestinal homeostasis.
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Change in body composition with skeletal muscle wasting, a major component of pulmonary cachexia, is associated with mortality in chronic obstructive pulmonary disease and cancer. However, its relevance in interstitial lung diseases (ILDs) remains unclear. We hypothesized changes in body composition would be associated with mortality in ILDs. ⋯ Distinct changes in body composition had prognostic significance among patients with IPF and iPPFE. Lower ESMCSA and ESMMA were independently associated with poor prognosis in IPF and iPPFE, respectively. These results suggest values to measure body composition changes in managing patients with IPF and iPPFE.
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Pediatric high-grade brain tumors and adult glioblastoma are associated with significant morbidity and mortality. Oncolytic herpes simplex virus-1 (oHSV) is a promising approach to target brain tumors; oHSV G207 and M032 (encodes human interleukin-12) are currently in phase I clinical trials in children with malignant supratentorial brain tumors and adults with glioblastoma, respectively. We sought to compare the sensitivity of patient-derived pediatric malignant brain tumor and adult glioblastoma xenografts to these clinically-relevant oHSV. ⋯ Differences in sensitivity may be due in part to nectin-1 expression, which predicted responses to the viruses. Treatment with oHSV resulted in prolonged survival in both pediatric and adult intracranial patient-dervied tumor xenograft models. Our results suggest that pediatric brain tumors are ideal targets for oHSV and that brain tumor expression of nectin-1 may be a useful biomarker to predict patient response to oHSV.
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Meta Analysis
Impact of timing of surgery in elderly hip fracture patients: a systematic review and meta-analysis.
We aimed to assess the impact of timing of surgery in elderly patients with acute hip fracture on morbidity and mortality. We systematically searched MEDLINE, the Cochrane Library, Embase, PubMed, and trial registries from 01/1997 to 05/2017, as well as reference lists of relevant reviews, archives of orthopaedic conferences, and contacted experts. Eligible studies had to be randomised controlled trials (RCTs) or prospective cohort studies, including patients 60 years or older with acute hip fracture. ⋯ No statistical significant different mortality risk was observed when comparing patients operated on within or after 24 hours (RR 0.82, 95% CI 0.67-1.01). Adjusted data demonstrated fewer complications (8% vs. 17%) in patients who had early surgery, and increasing risk for pressure ulcers with increased time of delay in another study. Early hip surgery within 48 hours was associated with lower mortality risk and fewer perioperative complications.