Exploring the Efficacy of Selected Allografts in Chronic Wound Healing: Evidence from Murine Models and Clinical Data for a Proposed Treatment Algorithm.

Significance: Chronic wounds can lead to poor outcomes for patients, with risks, including amputation and death. In the United States, chronic wounds affect 2.5% of the population and cost up to $28 billion per year in primary health care costs. Recent Advances: Allograft tissues (dermal, amnion, and amnion/chorion) have shown efficacy in improving healing of chronic, recalcitrant wounds in human patients, as evidenced by multiple clinical trials. Their mechanisms of actions have been relatively understudied, until recently. Research in murine models has shown that dermal allografts promote reepithelialization, amnion allografts promote granulation tissue formation and angiogenesis, and amnion/chorion allografts support all stages of wound healing. These findings confirm their effectiveness and illuminate their therapeutic mechanisms. Critical Issues: Despite the promise of allografts in chronic wound care, a gap exists in understanding which allografts are most effective during each wound healing stage. The variable efficacy among each type of allograft suggests a mechanistic approach toward a proposed clinical treatment algorithm, based on wound characteristics and patient's needs, may be beneficial. Future Directions: Recent advances in allografts provide a framework for further investigations into patient-specific allograft selection. This requires additional research to identify which allografts support the best outcomes during each stage of wound healing and in which wound types. Longitudinal human studies investigating the long-term impacts of allografts, particularly in the remodeling phase, are also essential to developing a deeper understanding of their role in sustained wound repair and recovery.

Anti-fibrotic effects of statin drugs: A review of evidence and mechanisms.

Fibrosis is a pathological repair process common among organs, that responds to tissue damage by replacement with non-functional connective tissue. Despite the widespread prevalence of tissue fibrosis, manifesting in numerous disease states across myriad organs, therapeutic modalities to prevent or alleviate fibrosis are severely lacking in quantity and efficacy. Alongside development of new drugs, repurposing of existing drugs may be a complementary strategy to elect anti-fibrotic compounds for pharmacologic treatment of tissue fibrosis. Drug repurposing can provide key advantages to de novo drug discovery, harnessing the benefits of previously elucidated mechanisms of action and already existing pharmacokinetic profiles. One class of drugs with a wealth of clinical data and extensively studied safety profiles is the statins, a class of antilipidemic drugs widely prescribed for hypercholesterolemia. In addition to these widely utilized lipid-lowering effects, increasing data from cellular, pre-clinical mammalian, and clinical human studies have also demonstrated that statins are able to alleviate tissue fibrosis originating from a variety of pathological insults via lesser-studied, pleiotropic effects of these drugs. Here we review literature demonstrating evidence for direct effects of statins antagonistic to fibrosis, as well as much of the available mechanistic data underlying these effects. A more complete understanding of the anti-fibrotic effects of statins may paint a clearer picture of their anti-fibrotic potential for various clinical indications. Additionally, more lucid comprehension of the mechanisms by which statins exert anti-fibrotic effects may aid in development of novel therapeutic agents that target similar pathways but with greater specificity or efficacy.

Concept Inventories as a Complement to Learning Progressions.

Learning progressions (LPs) are descriptions of students' growing sophistication in the understanding of a particular construct through a curricular sequence. They are particularly useful for organizing complex constructs for which students do not necessarily connect concepts as taught in different courses. However, they are challenging to construct, because they attempt to linearize students' inherently nonlinear learning. As a result, it is essential to have methods to assess students' arrival at particular steps along the progression. One tool readily available to instructors is concept inventories (CIs). We have mapped published CIs to LPs for acid-base chemistry. The alignment not only provides an assessment that professors can use to pinpoint student learning, but also creates another tool to verify hypothetical LPs.  We have compared the types of questions asked on CIs in chemistry, biology, and biochemistry, as well as in some standardized test banks. The mapping of questions from CIs to steps on the LPs allows refinement of the LPs and reveals gaps in assessment tools for sophisticated concepts. This alignment is a novel addition to the cycle of validation of an LP.