Fitting form to function: reorganization of faculty roles for a new dental curriculum and its governance.

The College of Dentistry at the University of Illinois at Chicago has reorganized its predoctoral curriculum to better integrate biomedical, clinical, and behavioral sciences using a systems-based framework. The resulting D.M.D. curriculum features small-group discussions of patient scenarios that include orofacial, systemic, and professionalism learning objectives. Small-group learning is closely coordinated with laboratory, pre-patient care, and patient care experiences. Accordingly, the college has also reorganized its faculty roles to eliminate discipline-based silos and to better ensure program coherence. The new organizational structure is designed to improve coordination among faculty course teams that develop and administer individual courses, several units that provide curriculum resources and support services, and the curriculum committee, which is charged with governance of the curriculum as a whole. In addition, the new structure employs a system of reporting and planning relationships to ensure continuous monitoring and improvement of the curriculum. This article describes six principles that guide the new faculty roles structure, defines the various faculty roles and their coordinating relationships, presents diagrams depicting the organizational structures for curriculum governance, administration, and support, and discusses mechanisms for faculty support and continuous curriculum improvement.

Modulation of C1-Inhibitor and Plasma Kallikrein Activities by Type IV Collagen.

The contact system of coagulation can be activated when in contact with biomaterials. As collagen is being tested in novel biomaterials in this study, we have investigated how type IV collagen affects plasma kallikrein and C1-inhibitor. Firstly, we showed C1-inhibitor binds to type IV collagen with a Kd of 0.86 µM. The effects of type IV collagen on plasma kallikrein, factor XIIa, and ß-factor XIIa activity and on C1-inhibitor function were determined. Factor XIIa rapidly lost activity in the presence of type IV collagen, whereas plasma kallikrein and ß-factor XIIa were more stable. The rate of inhibition of plasma kallikrein by C1-inhibitor was decreased by type IV collagen in a dose-dependent manner. These studies could be relevant to the properties of biomaterials, which contain collagen, and should be considered in the testing for biocompatibility.

Maximising the potential of part-time clinical teachers.

BACKGROUND: A problem faced by health professions education throughout the world is a lack of full-time clinical teachers. This is particularly serious in dentistry and nursing, but is increasingly also true in medicine. To make up for this shortfall there is a growing reliance on part-time clinical teachers. CONTEXT: Part-time clinical teachers are essential for the education of students. However, compared with their full-time counterparts, the part-time teachers are often not adequately prepared for their roles as educators within the context of the clinical curriculum. They might not be trained in the latest educational practices, and may be unprepared for the time needed to excel as teachers and mentors. IMPLICATIONS: As part-time teachers take on more responsibility, it is important that they take part in orientation and training sessions to assist them in developing the skills they need to succeed. This will require a significant commitment from the institution as well as the part-time teacher, but is critical for maintaining the academic quality of the clinical training programmes. This also represents an untapped area for research into how to ensure the success of part-time clinical teachers.

Estimating the additional cost of disability: beyond budget standards.

Disabled people have long advocated for sufficient resources to live a life with the same rights and responsibilities as non-disabled people. Identifying the unique resource needs of disabled people relative to the population as a whole and understanding the source of these needs is critical for determining adequate levels of income support and for prioritising service provision. Previous attempts to identify the resources and costs associated with disability have tended to rely on surveys of current resource use. These approaches have been criticised as being inadequate for identifying the resources that would be required to achieve a similar standard of living to non-disabled people and for not using methods that are acceptable to and appropriate for the disabled community. The challenge is therefore to develop a methodology that accurately identifies these unique resource needs, uses an approach that is acceptable to the disabled community, enables all disabled people to participate, and distinguishes 'needs' from 'wants.' This paper describes and presents the rationale for a mixed methodology for identifying and prioritising the resource needs of disabled people. The project is a partnership effort between disabled researchers, a disability support organisation and academic researchers in New Zealand. The method integrates a social model of disability framework and an economic cost model using a budget standards approach to identify additional support, equipment, travel and time required to live an 'ordinary life' in the community. A survey is then used to validate the findings and identify information gaps and resource priorities of the community. Both the theoretical basis of the approach and the practical challenges of designing and implementing a methodology that is acceptable to the disabled community, service providers and funding agencies are discussed.

Constructive Functional Diversity: a new paradigm beyond disability and impairment.

AIMS OF THE PAPER: This article presents a more dynamic and constructive paradigm than the current dominant ones (for example medical or social models), to describe and change the impact of impairment and disability. The reflections contained are inspired by personal and professional frustration with the existing polarized ideology of human function, which fails to adequately describe the diversity of physiological and psychosocial function amongst people. It aims to provoke and inspire dialogue about our current paradigm of human function in relation to value and capacity. KEY FINDINGS AND IMPLICATIONS: Within this paper: I critique society's biases regarding of functional deficit relative to the subconscious fear of losing function; I question the polarity of the negatively framed language of impairment and disability; I offer constructive, creative 'solutions' to describe the experience of atypical function. In so doing, an entirely new language of diverse human function and a concept of Constructive Functional Diversity (CFD) is proposed, which includes a complex yet logical array of modes and outcomes of function. CONCLUSIONS AND RECOMMENDATIONS: Finally I suggest the benefits of a more dynamic paradigm of functional change in enhancing rehabilitative outcomes, including client-directed practice.

Curriculum restructuring at a North American dental school: rationale for change.

The purpose of this article is to discuss how traditional dental school curricula are inconsistent with research in how learners learn. In the last ten years, there has been considerable discussion about the need for dental education reform, and innovative changes have occurred in the curricula of a number of U.S. dental schools. However, efforts in curriculum restructuring have been hindered by the lack of evidence that one specific curriculum design achieves outcomes superior to other designs. Moreover, there has been little discussion in the dental literature about how modern theories of learning can provide a sound rationale for change in dental education. Thus, it is important for those involved in curriculum reform to present the rationale for change based on the best available evidence. In this review, we summarize aspects of research on learning that seem applicable to dental education and outline ways in which curricula might be changed to become more consistent with the evidence.

Expression of matrix metalloproteinase genes in the rat intramembranous bone during postnatal growth and upon mechanical stresses.

A cranial suture consists of neural-crest derived cells and matrices between mineralized skull bones. Little is known regarding the involvement of matrix metalloproteinases (MMPs) in the degradation of extracellular matrix of cranial sutures. In the postnatal rat model, the posterior frontal suture (PFS) undergoes complete ossification between P12-P22, whereas the sagittal suture (SS) remains patent. The present study utilized reverse transcriptase-polymerase chain reaction (RT-PCR) to explore the expression of MMP-1 and MMP-2 genes in the PFS and SS in P8 and P32 rats, and also to determine whether these MMP genes are modulated by exogenous mechanical forces. RNA was isolated from P8 and P32 normal PFS and SS each by pooling sutural specimens from 14 to 20 rats. RT-PCR analysis and semi-quantitative luminosity demonstrated the expression of MMP-1 and MMP-2 genes in the patent P8 PFS, P8 SS, and P32 SS, but no apparent MMP-2 expression in the physiologically ossified P32 PFS. Exogenous cyclic forces applied to the maxilla at 1000 mN and 4 Hz elicited corresponding cyclic bone strain waveforms with peak strain of 134.14+/-38.15 muepsilon (mean+/-S.D.) for the PFS, and 28.35+/-10.86 muepsilon for the SS in P32 rats. These cyclic forces delivered for 20 min/d over 2 consecutive days induced the expression of MMP-2 gene in the physiologically fused P32 PFS that was not expressed without mechanical stresses. Taken together, these data suggest potentially important roles of MMP genes in the postnatal development of cranial sutures, and their susceptibility to mechanical stresses.

Inhibition of plasma kallikrein by C1-inhibitor: role of endothelial cells and the amino-terminal domain of C1-inhibitor.

Activation of plasma prekallikein and generation of bradykinin are responsible for the angioedema attacks observed with C1-inhibitor deficiency. Heterozygous individuals with <50% levels of active C1-inhibitor are susceptible to angioedema attacks indicating a critical need for C1-inhibitor to be present at maximum levels to prevent unwanted prekallikrein activation. Studies with purified proteins do not adequately explain this observation. Therefore to investigate why reduction of C1-inhibitor to levels seen in angioedema patients results in excessive kallikrein generation we examined the effect of endothelial cells on the inhibition of kallikrein by C1-inhibitor. Surprisingly, it was found that a C1-inhibitor concentration of greater than 1 microM was needed to inhibit 3 nM kallikrein. We propose that this apparent protection from inhibition was mediated by kallikrein binding to the cells via the heavy chain in a high molecular weight kininogen and zinc independent manner. Protection of kallikrein from inhibition was not observed when C1-inhibitor truncated in the amino-terminal domain by the StcE metalloproteinase was used, which suggests a novel function for this unique domain. The requirement for high concentrations of C1-inhibitor to fully inhibit kallikrein is consistent with the fact that reduced levels of C1-inhibitor result in the kallikrein activation seen in angioedema.

Serpin-ligand interactions.

One of the more common features of serpins is the ability to bind various ligands. Ligand binding can occur so that the inhibitory properties of the serpin are regulated, so that the serpin can be localized, or to produce or modulate some other biological function of the serpin. Ligands known to affect serpin biologic activity include glycosaminoglycans such as heparin, heparan sulfate and dermatan sulfate, DNA, extracellular matrix proteins such as vitronectin and collagen, and small organic molecule hormones. Many different biochemical and biophysical techniques in conjunction with molecular biology and cell biology approaches have been used to study the binding of various ligands to serpins and to assess the influence of this binding on activity and structure. We summarize here the different approaches that have been used to identify serpin ligands and the many methods that have been used to characterize the interactions of these ligands with their cognate serpins.

Characterization of different high molecular weight angiotensinogen forms.

BACKGROUND: Angiotensinogen is the substrate for renin in the system that releases angiotensin II. This renin-angiotensin system is an important regulator of blood pressure (BP), and defects in the system are linked to the development of hypertension. Native angiotensinogen is a 62,000-dalton monomer, but various high molecular weight forms also exist, which have not been well characterized. High molecular weight angiotensinogen has been reported to be 5% of the total angiotensinogen, and increases to 60% of the total during pregnancy and hypertension. The purpose of this investigation was to study high molecular weight angiotensinogen in normal plasma. METHODS: Normal human plasma was run on a gel filtration column, and high molecular weight angiotensinogen detected by Western blotting. Further purification was by ion-exchange chromatography. In vitro polymerization of angiotensinogen was analyzed by sodium dodecyl sulfate (SDS) and native gels. RESULTS: Two forms of high molecular weight angiotensinogen were found with molecular weights of 500,000 and 250,000 daltons on gel filtration, and 140,000 and 110,000 daltons, respectively, on nonreduced SDS-polyacrylamide gel electrophoresis, and at 62,000 daltons on reduced gels. Our estimation of the amount of high molecular weight angiotensinogen present is close to that reported previously. We also describe some of the in vitro polymerization characteristics of angiotensinogen, which can be explained by angiotensinogen being a member of the serpin family of proteins. CONCLUSIONS: The angiotensinogen polymers produced in vitro might provide a model system for some of the high molecular weight forms produced in vivo, and help in understanding their function.

alpha(1)-Proteinase inhibitor mutants with specificity for plasma kallikrein and C1s but not C1.

Coagulation and complement proteinases are activated in sepsis, and one approach to therapy is to develop proteinase inhibitors that will specifically inhibit these proteinases without inhibiting activated protein C, a proteinase that is beneficial to survival. In this study, we made mutants of the serpin alpha(1)-PI, designed to mimic the specificity of C1-inhibitor. The P3-P2-P1 residues of alpha1-PI were changed from IPM to LGR and PFR, sequences preferred by C1s and kallikrein, respectively. Inhibition of C1s, kallikrein, factor XIIa, and activated protein C was assessed by SDS-PAGE, and by determination of the k(app) and SI. alpha(1)-PI-LGR inhibited C1s with a rate of 7790 M(-1)s(-1), but only minimal inhibition of C1 in a hemolytic assay was observed. Kallikrein, factor XIIa, and activated protein C were inhibited with rates of 382,180 M(-1)s(-1), 10,400 M(-1)s(-1), and 3500 M(-1)s(-1), respectively. alpha(1)-PI-PFR was a poor inhibitor of C1s, factor XIIa, and activated protein C, but had enhanced reactivity with kallikrein. Changing the P4' residue of alpha(1)-PI-LGR Pro to Glu reduced the activity with C1s, consistent with the idea that C1s requires hydrophobic residues in this region of the serpin for optimal interaction. The data provide insight into the requirements for kallikrein and C1s inhibition necessary for designing inhibitors with appropriate properties for further investigation as therapeutic agents.

Release and degradation of angiotensin I and angiotensin II from angiotensinogen by neutrophil serine proteinases.

Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen. The relative order of potency in releasing angiotensin II by the three proteinases at equivalent concentrations is cathepsin G > elastase > proteinase 3. When all three proteinases are used together, the release of angiotensin II is greater than the sum of the release when each proteinase is used individually. Cathepsin G and elastase can also degrade angiotensin II, reactions which might be important in regulating the activity of angiotensin II. The release and degradation of angiotensin II by the neutrophil proteinases are reactions which could play a role in the local inflammatory response and wound healing.