Redistribution of the chromatin remodeler Brg1 directs smooth muscle-derived adventitial progenitor-to-myofibroblast differentiation and vascular fibrosis.

Vascular smooth muscle-derived Sca1+ adventitial progenitor (AdvSca1-SM) cells are tissue-resident, multipotent stem cells that contribute to progression of vascular remodeling and fibrosis. Upon acute vascular injury, AdvSca1-SM cells differentiate into myofibroblasts and are embedded in perivascular collagen and the extracellular matrix. While the phenotypic properties of AdvSca1-SM-derived myofibroblasts have been defined, the underlying epigenetic regulators driving the AdvSca1-SM-to-myofibroblast transition are unclear. We show that the chromatin remodeler Smarca4/Brg1 facilitates AdvSca1-SM myofibroblast differentiation. Brg1 mRNA and protein were upregulated in AdvSca1-SM cells after acute vascular injury, and pharmacological inhibition of Brg1 by the small molecule PFI-3 attenuated perivascular fibrosis and adventitial expansion. TGF-ß1 stimulation of AdvSca1-SM cells in vitro reduced expression of stemness genes while inducing expression of myofibroblast genes that was associated with enhanced contractility; PFI blocked TGF-ß1-induced phenotypic transition. Similarly, genetic knockdown of Brg1 in vivo reduced adventitial remodeling and fibrosis and reversed AdvSca1-SM-to-myofibroblast transition in vitro. Mechanistically, TGF-ß1 promoted redistribution of Brg1 from distal intergenic sites of stemness genes and recruitment to promoter regions of myofibroblast-related genes, which was blocked by PFI-3. These data provide insight into epigenetic regulation of resident vascular progenitor cell differentiation and support that manipulating the AdvSca1-SM phenotype will provide antifibrotic clinical benefits.

Video corroboration of player incurred impacts using trunk worn sensors among national ice-hockey team members.

PURPOSE: Video corroboration of player incurred impacts (PII) using trunk-worn wearable sensors (WS) among national ice-hockey team members. METHODS: 23 members of the U.S. National (NTDP) U18 team consented to procedures approved by EMU Human Subjects Committee. Bioharness-3 (Zephyr, MD) WS recorded occurrences of PII during games and impacts were generated using Impact Processor (Zephyr, MD). Eight players with the top activity levels each game determined by WS, were observed using video and synchronized with game video collected by NTDP staff. Impacts identified by WS of 6-7.9 g (Z3), 8-9.9 g (Z4) and 10+ g (Z5) were used to corroborate PII. Magnitude and duration of each identified impact were compared by category using MANOVA with Tukey post hoc (α = 0.05; SPSS 22.0, IBM, NY). RESULTS: Of 419 on-ice impacts, 358 were confirmed true PII (85.5%), 60 as other non-PII (14.3%) and 1 false positive (0.2%). For 358 PII, 17 (4.1%) were 1) Board contact/no check, 74 (17.7%), 2) Board contact/check, 202 (48.2%), 3) Open ice check, 65 (15.5%), 4) Player fall. Of 60 Non-PII, 19 (4.5%) as 5) other form of player to player event, 16 (3.8%) as 6) Hard Stop, 19 (4.5%) as 7) Slapshots and 6 (1.4%) as 8) other identifiable player events. 160 of the 200 Z3 events were PII (80%), 103 of 110 Z4 events (93.6%) and 95 of 109 Z5 events were PII (87.2%). The magnitude of impacts was not different by category, but the duration of category 6 (Hard stop; .058 s) was lower than categories 2, 4 and 7 (.112, .112, .133 s, respectively, p < .05). CONCLUSION: These data show that using some limited criteria (e.g. impact magnitude and duration), PII can be identified with relatively high accuracy in ice hockey using trunk-worn wearable sensors.

Proposal and Validation of a Knee Measurement System for Patients With Osteoarthritis.

OBJECTIVE: Currently most measurements of knee joint function are obtained through observation and patient-reported outcomes. This paper proposes an implementation and validation of a knee monitor to measure quantitative joint data in multiple degrees of freedom. The proposed system is configurable with minimal patient interaction and no frame-alignment calibration procedure is required for measurement after visually placing/replacing sensors on patients. METHODS: A mobile software system was developed using a method of extracting clinical knee angles based on attitude estimations from independent wearable sensors. Validation was performed using a robot phantom and results were compared with a gold standard motion capture system. Two instrumentation placements (lateral and posterior) were examined. RESULTS: A posterior sensor placement was determined to provide the most repeatable results through multiple degrees of freedom and measurement accuracy approached a gold standard motion capture technology with low root-mean-square error (flexion: 3.34°, internal/external rotation: 2.18°, and varus/valgus: 1.44°). CONCLUSION: The proposed system is simple to use and convenient for use in ambulatory or unsupervised environments for joint measurement; however, it was shown that accuracy can be sensitive to sensor placement. SIGNIFICANCE: This system would be beneficial for obtaining quantitative patient data or tracking functional activity in variable environments, providing clinicians with indications of how patients' knees function during activity, potentially permitting more individualized care and recommendations.

Challenges in Obtaining HIV Testing in an Acute Involuntary Inpatient Psychiatric Setting.

Even in health care professions, a stigma remains for patients with co-occurring HIV and serious mental illness. Researchers at a large, urban medical center encountered this stigma when they attempted to initiate a study of cognition in psychiatric inpatients with and without HIV who were seen as vulnerable in the context of research. Education efforts and advocacy on the part of the research team was instrumental and resulted in system-wide changes in the hospital, including the addition of HIV testing to the psychiatric admission laboratory panel. Within the first year that routine laboratory orders included an HIV test, the rate of testing ordered by inpatient-attending psychiatrists reached 60% of admissions. As of 2014, 13 HIV tests were found to be HIV seropositive in inpatients, with four of those cases classified as new-onset, as opposed to two positive tests in the year prior to our study.

Postoperative cognitive dysfunction after noncardiac surgery: effects of metabolic syndrome.

PURPOSE: Vascular risk factors, including metabolic syndrome, are known to contribute to the development of cognitive dysfunction. We tested the hypothesis that patients with metabolic syndrome are more likely to develop cognitive dysfunction after noncardiac surgery. METHODS: Age- and education-balanced patients (n = 60) undergoing elective noncardiac surgery with and without metabolic syndrome and 30 nonsurgical controls were enrolled. Recent verbal and nonverbal memory and executive functions were assessed using a psychometric test battery before and 1 month after noncardiac surgery or at a 1-month interval in nonsurgical controls. RESULTS: Neurocognitive scores under baseline conditions were similar in surgical patients with versus without metabolic syndrome in all examined cognitive modalities (recent nonverbal and verbal memory, executive functions). Pronounced reductions in tests of verbal memory (delayed story recall, immediate and delayed word list recall) and executive function (backward digit span) were observed in patients with versus without metabolic syndrome after surgery. Overall cognitive performance after surgery was also significantly (P = 0.03) more impaired in patients with versus without metabolic syndrome. The prevalence rate of POCD wasdifferent in the studied groups (17/30 [corrected] and 8/30 in patientswith versus without metabolic syndrome; P < 0.02). CONCLUSIONS: The results indicate that cognitive functions were more profoundly impaired in patients with metabolic syndrome undergoing noncardiac surgery compared with their healthier counterparts.