AimFibrosis is the most common complication from chronic diseases, and yet no therapy capable of mitigating its effects is available. Our goal is to unveil specific signallings regulating the fibrogenic process and to identify potential small molecule candidates that block fibrogenic differentiation of fibro/adipogenic progenitors.MethodWe performed a large-scale drug screen using muscle-resident fibro/adipogenic progenitors from a mouse model expressing EGFP under the Collagen1a1 promotor. We first confirmed that the EGFP was expressed in response to TGFβ1 stimulation in vitro. Then we treated cells with TGFβ1 alone or with drugs from two libraries of known compounds. The drugs ability to block the fibrogenic differentiation was quantified by imaging and flow cytometry. From a two-rounds screening, positive hits were tested in vivo in the mice model for the Duchenne muscular dystrophy (mdx mice). The histopathology of the muscles was assessed with picrosirius red (fibrosis) and laminin staining (myofiber size).Key findingsFrom the in vitro drug screening, we identified 21 drugs and tested 3 in vivo on the mdx mice. None of the three drugs significantly improved muscle histopathology.SignificanceThe in vitro drug screen identified various efficient compounds, none of them strongly inhibited fibrosis in skeletal muscle of mdx mice. To explain these observations, we hypothesize that in Duchenne Muscular Dystrophy, in which fibrosis is a secondary event due to chronic degeneration and inflammation, the drugs tested could have adverse effect on regeneration or inflammation, balancing off any positive effects and leading to the absence of significant results.
The effects of tert-butylation of tryptophan residues in peptide chains on the enzymatic digestibility were investigated. It was shown that replacement of tryptophan in position 9 of Corticotropin-(1--19)-nonadecapeptidamide by a mono- or tri-tert-butylated tryptophan enhances the resistance of the resulting analogue against proteolytic enzymes.
Delirium is often misdiagnosed in dementia and mistreated with medications that may be continued even after hospital discharge. This paper will present results from the Early Nurse Detection of Delirium Superimposed on Dementia (END-DSD) NIH funded cluster randomized trial. We hypothesized that subjects on the END-DSD units would receive fewer psychoactive medications compared to subjects on control units. Participants (n = 391; M age = 84; 71% female; 95% Caucasian) were enrolled at the time of admission. The intervention group had significantly lower number of medications given PRN than the control group. The number of unique Beers medications given PRN was lower in the intervention group. And the number of PRN medications with an anticholinergic burden score of 3 was significantly lower. These drugs negatively impact older adults and should be avoided. Nurses play an integral role in decreasing the use of PRN and psychoactive medications in older adults. IMPROVING MEDICATION SAFETY AND TRAINING FOR OLDER ADULTS WITH DEMENTIA N. Brandt, University of Maryland at Baltimore, Baltimore, MarylandThe intent of this session is to highlight the work of an interprofessional team and tactics to improve medication safety for older adults and their caregivers. Interprofessional health care providers at the Baltimore Veterans Affairs Medical Clinic, namely medicine, pharmacy, nursing, neuropsychology & social work, have been actively involved in various clinical and educational initiatives. One of these initiatives is the "DEMO: Dementia Evaluation, Management and Outreach" program. This program aims to extend dementia evaluations to regional community-based outpatient clinics, which serve people in more rural regions, and to improve management and follow-up of these patients, including medication coordination and adherence monitoring. Additionally, the team has created and evaluated online interprofessional training focusing on medications and other needs of older adults with dementia, looking at knowledge, skills and attitudes. Results and resources will be shared with conference attendees that can be useful for their clinical care settings. Medication-related problems are common in older adults with multiple chronic conditions. Holistic, patient-centered approaches may be particularly well-suited to addressing the complex and disease-crossing nature of these problems. In this presentation, we will present results of a cluster-controlled clinical trial that evaluated the impact of a nursebased primary care intervention on medication outcomes in 1,218 high-risk older Israeli adults. Our primary outcome was the number of changes to patients' medication regimens, a marker of attention to patient-centered prescribing. After 9 months of follow-up, intervention subjects had more changes to their medication regimen than control subjects (mean 4.04 vs. 3.62 medication changes; adjusted difference 0.55, P=0.001). Similarly, intervention subjects had more changes to their symptomatic medications (mean 1.38 vs. 1.26 changes, adjus...
Background: Asian Woollyneck Ciconia episcopus is large wading bird whose conservation status has been recently down-listed, despite a lack of general knowledge on its nesting ecology and breeding success. Thus, in this study we conducted the most comprehensive survey on the nesting ecology of this species to date. Methods: We located 39 nesting sites across 18 districts of Nepal and recorded nest tree characteristics for the nine tree species they nested in. We also used Maxent modelling to further understand factors important for nesting habitat suitability and to identify new areas for future surveys. Results: They most commonly nested in Simal Bombax ceiba (n =21), followed by Sal Shorea robusta (n=6) and Salla Pinus roxburghii (n=4). The mean height of the nesting tree, nest height and tree diameter were 29.8 ± 5.8m (±SD), 1.03 ± 0.35m & 25.3 ± 5.8 m respectively. Nesting and fledging success were additionally recorded from 31 nesting attempts at 19 of these nesting sites between 2016 and 2020. Woollyneck had an estimated nesting success probability of 0.81 ± 0.07 and a mean fledging success of 1.94 ± 0.25 (±SE) chicks per nest. MaxEnt modelling identified a total potential suitable nesting habitat area of 9.64 % (14228km2) of total area in Nepal, with this located within 72 districts (out of 77), mostly in the western part of Nepal. The modelling parameters suggest that slope, land-use, precipitation and forest were important determinants of nesting habitat suitability. Conclusions: The most likely district reported by the model for Woollyneck nesting habitat has not previously reported nests which suggests additional survey effort in this region is warranted. We recommend that priority should be given to conserve taller trees close to settlements and cropland, and future studies should consider the potential impact of climate change on nesting suitability of this species.
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