Search

Spreading depolarizations (SDs) are profound disruptions of cellular homeostasis that slowly propagate through gray matter and present an extraordinary metabolic challenge to brain tissue. Recent work has shown that SDs occur commonly in human patients in the neurointensive care setting and have established a compelling case for their importance in the pathophysiology of acute brain injury. The International Conference on Spreading Depolarizations (iCSD) held in Boca Raton, Florida, in September of 2018 included a discussion session focused on the question of "Which SDs are deleterious to brain tissue?" iCSD is attended by investigators studying various animal species including invertebrates, in vivo and in vitro preparations, diseases of acute brain injury and migraine, computational modeling, and clinical brain injury, among other topics. The discussion included general agreement on many key issues, but also revealed divergent views on some topics that are relevant to the design of clinical interventions targeting SDs. A draft summary of viewpoints offered was then written by a multidisciplinary writing group of iCSD members, based on a transcript of the session. Feedback of all discussants was then formally collated, reviewed and incorporated into the final document. It is hoped that this report will stimulate collection of data that are needed to develop a more nuanced understanding of SD in different pathophysiological states, as the field continues to move toward effective clinical interventions.

Founded by Eunice Kennedy Shriver, Community of Caring fosters in staff and students an increased sense of family and family-member responsibility; demonstration of mutual respect, trust, moral consciousness, individual responsibility; and a sense of caring and helping others through community service. Program components and benefits are discussed. (MLH)

Transforming growth factor-[[beta].sub.1] (TGF-[[beta].sub.1]) signal and downstream Smads play an important role in tissue fibrosis and matrix remodeling in various etiologies of heart failure. Inhibitory Smad7 (I-Smad7) is an inducible regulatory Smad protein that antagonizes TGF-[[beta].sub.1] signal mediated via direct abrogation of R-Smad phosphorylation. The effect of ectopic I-Smad7 on net collagen production was investigated using hydroxyproline assay. Adenovirus-mediated I-Smad7 gene (at 100 multiplicity of infection) transfer was associated with significant decrease of collagen synthesis in the presence and absence of TGF-[[beta].sub.1] in primary rat cardiac myofibroblasts. In I-Smad7-infected cells, we also observed the ablation of TGF-[[beta].sub.1]-induced R-Smad2 phosphorylation vs. LacZ controls. Overdriven I-Smad7 was associated with significantly increased expression of immunoreactive 65-kDa matrix metalloproteinase-2 (MMP-2) protein in culture medium of myofibroblast compared with LacZ-infected cells. Expression of the 72-kDa MMP-2 variant, e.g., the inactive form, was not altered by exogenous I-Smad7 transfection/overexpression. Furthermore, I-Smad7 overexpression was associated with a significant increase and decrease in expression of p27 and phospho-Rb protein, respectively, as well as reduced [[sup.3]H]thymidine incorporation vs. Ad-LacZ-infected controls. We suggest that negative modulation of R-Smad phosphorylation by ectopic I-Smad7 may contribute to the downregulation of collagen in cardiac myofibroblasts and may suppress the proliferation of these cells. Thus treatments targeting the collagen deposition by overexpression of I-Smad7 may provide a new therapeutic strategy for cardiac fibrosis. myofibroblast; cardiac remodeling; matrix metalloproteinase; p27; fibroblast proliferation; cardiac fibrosis

ABSTRACT This paper examines the effect of both quality operations and high performance work system (HPWS) practices on firm performance for 1200 small manufacturers wanting to market their products to [...]

Objective: To determine whether use of a protective cover would affect temporospatial gait or ground reaction force (GRF) measurements obtained from dogs walking on a validated pressure-sensitive walkway (PSW). Animals: 5 healthy dogs. Procedures: In a crossover study design, all dogs were walked across a calibrated PSW with and without a protective cover in place in random order. Temporospatial gait data and GRFs obtained with and without the cover in place were compared. Results: No significant differences were identified in temporospatial gait measurements obtained with versus without the cover in place. The bias was low for all variables, and the 95% limits of agreement included 0. In contrast, significant differences were found between measurements obtained with versus without the cover in place for most GRFs, with measurements obtained with the cover in place significantly lower than those obtained without a cover. Clinical relevance: Results suggested that for dogs walking over a PSW, GRFs, but not temporospatial gait variables, would be significantly lower if a protective cover was placed over the walkway, compared with values obtained without a cover in place. [ABSTRACT FROM AUTHOR]