Review of Alterations in Perlecan-Associated Vascular Risk Factors in Dementia

Perlecan is a heparan sulfate proteoglycan protein in the extracellular matrix that structurally and biochemically supports the cerebrovasculature by dynamically responding to changes in cerebral blood flow. These changes in perlecan expression seem to be contradictory, ranging from neuroprotective and angiogenic to thrombotic and linked to lipid retention. This review investigates perlecan\u27s influence on risk factors such as diabetes, hypertension, and amyloid that effect Vascular contributions to Cognitive Impairment and Dementia (VCID). VCID, a comorbidity with diverse etiology in sporadic Alzheimer\u27s disease (AD), is thought to be a major factor that drives the overall clinical burden of dementia. Accordingly, changes in perlecan expression and distribution in response to VCID appears to be injury, risk factor, location, sex, age, and perlecan domain dependent. While great effort has been made to understand the role of perlecan in VCID, additional studies are needed to increase our understanding of perlecan\u27s role in health and in cerebrovascular disease

An Affordance-Based Methodology for Package Design

The term affordance describes an object\u27s utilitarian function or actionable possibilities. Product designers have taken great interest in the concept of affordances because of the bridge they provide relating to design, the interpretation of design and, ultimately, functionality in the hands of consumers. These concepts have been widely studied and applied in the field of psychology but have had limited formal application to packaging design and evaluation. We believe that the concepts related to affordances will reveal novel opportunities for packaging innovation. To catalyse this, presented work had the following objectives: (a) to propose a method by which packaging designers can purposefully consider affordances during the design process; (b) to explain this method in the context of a packaging-related case study; and (c) to measure the effect on package usability when an affordance-based design approach is employed

To See or Not to See: Do Front of Pack Nutrition Labels Affect Attention to Overall Nutrition Information?

Citation: Bix, L., Sundar, R. P., Bello, N. M., Peltier, C., Weatherspoon, L. J., & Becker, M. W. (2015). To See or Not to See: Do Front of Pack Nutrition Labels Affect Attention to Overall Nutrition Information? Plos One, 10(10), 20. doi:10.1371/journal.pone.0139732Background Front of pack (FOP) nutrition labels are concise labels located on the front of food packages that provide truncated nutrition information. These labels are rapidly gaining prominence worldwide, presumably because they attract attention and their simplified formats enable rapid comparisons of nutritional value. Methods Eye tracking was conducted as US consumers interacted with actual packages with and without FOP labels to (1) assess if the presence of an FOP label increases attention to nutrition information when viewers are not specifically tasked with nutrition-related goals; and (2) study the effect of FOP presence on consumer use of more comprehensive, traditional nutrition information presented in the Nutritional Facts Panel (NFP), a mandatory label for most packaged foods in the US. Results Our results indicate that colored FOP labels enhanced the probability that any nutrition information was attended, and resulted in faster detection and longer viewing of nutrition information. However, for cereal packages, these benefits were at the expense of attention to the more comprehensive NFP. Our results are consistent with a potential short cut effect of FOP labels, such that if an FOP was present, participants spent less time attending the more comprehensive NFP. For crackers, FOP labels increased time spent attending to nutrition information, but we found no evidence that their presence reduced the time spent on the nutrition information in the NFP. Conclusions The finding that FOP labels increased attention to overall nutrition information by people who did not have an explicit nutritional goal suggests that these labels may have an advantage in conveying nutrition information to a wide segment of the population. However, for some food types this benefit may come with a short-cut effect; that is, decreased attention to more comprehensive nutrition information. These results have implications for policy and warrant further research into the mechanisms by which FOP labels impact use of nutrition information by consumers for different foods

Measuring the effect of affordances on a crash cart medicine packaging

Abstract: In the United States, most drugs stored in crash carts of emergency rooms are packaged in folding cartons with opening mechanisms that involve pressing and tearing the bottom of the package. Anecdotal evidence and a previous study conducted by the research team suggest that these packages are counterintuitive for lay users. The concept of affordances, how design features communicate actionable possibilities, can be applied to improve the usability of packaging. In order to measure the effect of individual design features and previous experience on opening time and error frequency during first opening attempt, a commercially available package for epinephrine was redesigned and tested with two panels of participants; 33 lay users and 17 healthcare providers. Each experiment was conducted as a randomized complete block design with three factors: location of opening mechanism (top or bottom), type of opening mechanism (press-in or tab), and colour contrast in opening area (with and without). By crossing all possible conditions (2x2x2), eight different folding carton designs resulted. Each participant was treated as a block and presented all eight designs in a random order. Participants stood behind a counter of a fixed height and completed eight opening tasks in a lab facility (lay users) and an emergency room (healthcare providers). They were instructed to imagine an emergency scenario where they needed to remove all contents from each package as quickly as possible. Results show that colour contrast had no significant effect on opening time, having a tab significantly reduces time to open. More specifically, tabs cued the user as to the correct end containing the opening feature regardless of it was positioned on the top or bottom of the package. When there was no tab, then having the opening at the top resulted in a significant reduction in time to open, compared to having the opening at the bottom. In an analysis comparing the eight designs, the actual commercial packages ranked as the worst designs in terms of opening time and error frequency. Findings have critical implications for designing packages that are more usable and for eliminating errors during product use

Perlecan, a multi-functional, cell-instructive, matrix-stabilizing proteoglycan with roles in tissue development has relevance to connective tissue repair and regeneration

This review highlights the multifunctional properties of perlecan (HSPG2) and its potential roles in repair biology. Perlecan is ubiquitous, occurring in vascular, cartilaginous, adipose, lymphoreticular, bone and bone marrow stroma and in neural tissues. Perlecan has roles in angiogenesis, tissue development and extracellular matrix stabilization in mature weight bearing and tensional tissues. Perlecan contributes to mechanosensory properties in cartilage through pericellular interactions with fibrillin-1, type IV, V, VI and XI collagen and elastin. Perlecan domain I - FGF, PDGF, VEGF and BMP interactions promote embryonic cellular proliferation, differentiation, and tissue development. Perlecan domain II, an LDLR-like domain interacts with lipids, Wnt and Hedgehog morphogens. Perlecan domain III binds FGF-7 and 18 and has roles in the secretion of perlecan. Perlecan domain IV, an immunoglobulin repeat domain, has cell attachment and matrix stabilizing properties. Perlecan domain V promotes tissue repair through interactions with VEGF, VEGF-R2 and α2β1 integrin. Perlecan domain-V LG1-LG2 and LG3 fragments antagonize these interactions. Perlecan domain V promotes reconstitution of the blood brain barrier damaged by ischemic stroke and is neurogenic and neuroprotective. Perlecan-VEGF-VEGFR2, perlecan-FGF-2 and perlecan-PDGF interactions promote angiogenesis and wound healing. Perlecan domain I, III and V interactions with platelet factor-4 and megakaryocyte and platelet inhibitory receptor promote adhesion of cells to implants and scaffolds in vascular repair. Perlecan localizes acetylcholinesterase in the neuromuscular junction and is of functional significance in neuromuscular control. Perlecan mutation leads to Schwartz-Jampel Syndrome, functional impairment of the biomechanical properties of the intervertebral disc, variable levels of chondroplasia and myotonia. A greater understanding of the functional working of the neuromuscular junction may be insightful in therapeutic approaches in the treatment of neuromuscular disorders. Tissue engineering of salivary glands has been undertaken using bioactive peptides (TWSKV) derived from perlecan domain IV. Perlecan TWSKV peptide induces differentiation of salivary gland cells into self-assembling acini-like structures that express salivary gland biomarkers and secrete α-amylase. Perlecan also promotes chondroprogenitor stem cell maturation and development of pluripotent migratory stem cell lineages, which participate in diarthrodial joint formation, and early cartilage development. Recent studies have also shown that perlecan is prominently expressed during repair of adult human articular cartilage. Perlecan also has roles in endochondral ossification and bone development. Perlecan domain I hydrogels been used in tissue engineering to establish heparin binding growth factor gradients that promote cell migration and cartilage repair. Perlecan domain I collagen I fibril scaffolds have also been used as an FGF-2 delivery system for tissue repair. With the availability of recombinant perlecan domains, the development of other tissue repair strategies should emerge in the near future. Perlecan co-localization with vascular elastin in the intima, acts as a blood shear-flow endothelial sensor that regulates blood volume and pressure and has a similar role to perlecan in canalicular fluid, regulating bone development and remodeling. This complements perlecan’s roles in growth plate cartilage and in endochondral ossification to form the appendicular and axial skeleton. Perlecan is thus a ubiquitous, multifunctional, and pleomorphic molecule of considerable biological importance. A greater understanding of its diverse biological roles and functional repertoires during tissue development, growth and disease will yield valuable insights into how this impressive proteoglycan could be utilized successfully in repair biology

Quantifying Age-Related Differences in Information Processing Behaviors When Viewing Prescription Drug Labels

Adverse drug events (ADEs) are a significant problem in health care. While effective warnings have the potential to reduce the prevalence of ADEs, little is known about how patients access and use prescription labeling. We investigated the effectiveness of prescription warning labels (PWLs, small, colorful stickers applied at the pharmacy) in conveying warning information to two groups of patients (young adults and those 50+). We evaluated the early stages of information processing by tracking eye movements while participants interacted with prescription vials that had PWLs affixed to them. We later tested participants’ recognition memory for the PWLs. During viewing, participants often failed to attend to the PWLs; this effect was more pronounced for older than younger participants. Older participants also performed worse on the subsequent memory test. However, when memory performance was conditionalized on whether or not the participant had fixated the PWL, these age-related differences in memory were no longer significant, suggesting that the difference in memory performance between groups was attributable to differences in attention rather than differences in memory encoding or recall. This is important because older adults are recognized to be at greater risk for ADEs. These data provide a compelling case that understanding consumers’ attentive behavior is crucial to developing an effective labeling standard for prescription drugs

Processing of indexical information requires time: Evidence from change deafness

Studies of change detection have increased our understanding of attention, perception, and memory. In two innovative experiments we showed that the change detection phenomenon can be used to examine other areas of cognition—specifically, the processing of linguistic and indexical information in spoken words. One hypothesis suggests that cognitive resources must be used to process indexical information, whereas an alternative suggests that it is processed more slowly than linguistic information. Participants performed a lexical decision task and were asked whether the voice presenting the stimuli changed. Nonwords varying in their likeness to real words were used in the lexical decision task to encourage participants to vary the amount of cognitive resources/processing time. More cognitive resources/processing time are required to make a lexical decision with word-like nonwords. Participants who heard word-like nonwords were more likely to detect the change when it occurred (Experiment 1) and were more confident that the voice was the same when it did not change (Experiment 2). These results suggest that indexical information is processed more slowly than linguistic information and demonstrate how change detection can provide insight to other areas of cognition

Myc-induced nuclear antigen constrains a latent intestinal epithelial cell-intrinsic anthelmintic pathway

<div><p>Expulsion of parasitic gastrointestinal nematodes requires diverse effector mechanisms coordinated by a Th2-type response. The evolutionarily conserved JmjC protein; Myc Induced Nuclear Antigen (Mina) has been shown to repress IL4, a key Th2 cytokine, suggesting Mina may negatively regulate nematode expulsion. Here we report that expulsion of the parasitic nematode <i>Trichuris muris</i> was indeed accelerated in Mina deficient mice. Unexpectedly, this was associated not with an elevated Th2- but rather an impaired Th1-type response. Further reciprocal bone marrow chimera and conditional KO experiments demonstrated that retarded parasite expulsion and a normal Th1-type response both required Mina in intestinal epithelial cells (IECs). Transcriptional profiling experiments in IECs revealed anti-microbial α-defensin peptides to be the major target of Mina-dependent retention of worms in infected mice. In vitro exposure to recombinant α-defensin peptides caused cytotoxic damage to whipworms. These results identify a latent IEC-intrinsic anthelmintic pathway actively constrained by Mina and point to α-defensins as important effectors that together with Mina may be attractive therapeutic targets for the control of nematode infection.</p></div

Perlecan Maintains microvessel integrity in vivo and modulates their formation in vitro

Perlecan is a heparan sulfate proteoglycan assembled into the vascular basement membranes (BMs) during vasculogenesis. In the present study we have investigated vessel formation in mice, teratomas and embryoid bodies (EBs) in the absence of perlecan. We found that perlecan was dispensable for blood vessel formation and maturation until embryonic day (E) 12.5. At later stages of development 40% of mutant embryos showed dilated microvessels in brain and skin, which ruptured and led to severe bleedings. Surprisingly, teratomas derived from perlecan-null ES cells showed efficient contribution of perlecan-deficient endothelial cells to an apparently normal tumor vasculature. However, in perlecan-deficient EBs the area occupied by an endothelial network and the number of vessel branches were significantly diminished. Addition of FGF-2 but not VEGF165 rescued the in vitro deficiency of the mutant ES cells. Furthermore, in the absence of perlecan in the EB matrix lower levels of FGFs are bound, stored and available for cell surface presentation. Altogether these findings suggest that perlecan supports the maintenance of brain and skin subendothelial BMs and promotes vasculo- and angiogenesis by modulating FGF-2 function