Cross-linking density alters early metabolic activities in chondrocytes encapsulated in poly(ethylene glycol) hydrogels and cultured in the rotating wall vessel.

In designing a tissue engineering strategy for cartilage repair, selection of both the bioreactor, and scaffold is important to the development of a mechanically functional tissue. The hydrodynamic environment associated with many bioreactors enhances nutrient transport, but also introduces fluid shear stress, which may influence cellular response. This study examined the combined effects of hydrogel cross-linking and the hydrodynamic environment on early chondrocyte response. Specifically, chondrocytes were encapsulated in poly(ethylene glycol) (PEG) hydrogels having two different cross-linked structures, corresponding to a low and high cross-linking density. Both cross-linked gels yielded high water contents (92% and 79%, respectively) and mesh sizes of 150 and 60 A respectively. Cell-laden PEG hydrogels were cultured in rotating wall vessels (RWV) or under static cultures for up to 5 days. Rotating cultures yielded low fluid shear stresses (< or = 0.11 Pa) at the hydrogel periphery indicating a laminar hydrodynamic environment. Chondrocyte response was measured through total DNA content, total nitric oxide (NO) production, and matrix deposition for glycosaminoglycans (GAG). In static cultures, gel cross-linking had no effect on DNA content, NO production, or GAG production; although GAG production increased with culture time for both cross-linked gels. In rotating cultures, DNA content increased, NO production decreased, and overall GAG production decreased when compared to static controls for the low cross-linked gels. For the high cross-linked gels, the hydrodynamic environment had no effect on DNA content, but exhibited similar results to the low cross-linked gel for NO production, and matrix production. Our findings demonstrated that at early culture times, when there is limited matrix production, the hydrodynamic environment dramatically influences cell response in a manner dependent on the gel cross-linking, which may impact long-term tissue development.

Shifting the Curve: Fostering Academic Success in a Diverse Student Body.

PROBLEM: Diversity in the health care workforce is key to achieving health equity. Although U.S. medical schools have worked to increase the matriculation and academic success of underrepresented minority (URM) students (African Americans, Latinos, others), they have had only limited success. Lower standardized test scores, including on the Medical College Admission Test (MCAT), have been a barrier to matriculation for many URM applicants. Lower subsequent standardized exam scores, including on the United States Medical Licensing Exam Step 1, also have been an impediment to students' progress, with mean scores for URM students lagging behind those for others. APPROACH: Faculty at the Morehouse School of Medicine developed and implemented interventions to enhance the academic success of their URM students (about 75% are African American, and 5% are from other URM groups). To assess the outcomes of this work, the authors analyzed the MCAT scores and subsequent Step 1 scores of students in the graduating classes of 2009-2014. They also reviewed course evaluations, Graduation Questionnaires, and student and faculty interviews and focus groups. OUTCOMES: Students' Step 1 scores exceeded those expected based on their MCAT scores. This success was due to three key elements: (1) milieu and mentoring, (2) structure and content of the curriculum, and (3) monitoring. NEXT STEPS: A series of mixed-method studies are planned to better discern the core elements of faculty-student relationships that are key to students' success. Lower test scores are not a fixed attribute; with the elements described, success is attainable for all students.

Implementation and modification of an anatomy-based integrated curriculum.

Morehouse School of Medicine elected to restructure its first-year medical curriculum by transitioning from a discipline-based to an integrated program. The anatomy course, with regional dissection at its core, served as the backbone for this integration by weaving the content from prior traditional courses into the curriculum around the anatomy topics. There were four primary goals for this restructuring process. Goal 1: develop new integrated courses. Course boundaries were established at locations where logical breaks in anatomy content occurred. Four new courses were created, each containing integrated subject content. Goal 2: establish a curriculum management team. The team consisted of course directors, subject specialists, and a curriculum director. This team worked together to efficiently manage the new curriculum. Goal 3: launch contemporary examination and question banking methods. An electronic system, in which images could be included, was implemented for examinations and quizzes, and for storing and refining questions. Goal 4: ensure equitable distribution of standardized examinations and course grading systems among all courses. Assessments included quizzes, in-course examinations, and National Board of Medical Examiners® (NBME® ) Subject Examinations. A standard plan assigned the contribution of each to the final course grade. Significant improvement was seen on subject examinations. Once the obstacles and challenges of integration were overcome, a robust and efficient education program was developed. The curriculum is expected to continue evolving and improving, while retaining full regional dissection as a core element. Anat Sci Educ 10: 262-275. © 2016 American Association of Anatomists.

Clinical Correlations as a Tool in Basic Science Medical Education.

Clinical correlations are tools to assist students in associating basic science concepts with a medical application or disease. There are many forms of clinical correlations and many ways to use them in the classroom. Five types of clinical correlations that may be embedded within basic science courses have been identified and described. (1) Correlated examples consist of superficial clinical information or stories accompanying basic science concepts to make the information more interesting and relevant. (2) Interactive learning and demonstrations provide hands-on experiences or the demonstration of a clinical topic. (3) Specialized workshops have an application-based focus, are more specialized than typical laboratory sessions, and range in complexity from basic to advanced. (4) Small-group activities require groups of students, guided by faculty, to solve simple problems that relate basic science information to clinical topics. (5) Course-centered problem solving is a more advanced correlation activity than the others and focuses on recognition and treatment of clinical problems to promote clinical reasoning skills. Diverse teaching activities are used in basic science medical education, and those that include clinical relevance promote interest, communication, and collaboration, enhance knowledge retention, and help develop clinical reasoning skills.

Polyamines protect against radiation-induced oxidative stress.

Astronauts and cosmonauts are exposed to a wide variety of different hazards while in space that include radiation, which presents one of the most critical barriers to long-term missions. A major deleterious effect directly associated with ionizing radiation is the production of reactive oxygen species (ROS) such as peroxides and hydroxyl radicals. The free radicals generated by ultraviolet (UV) or ionizing radiation can attack cellular lipids, proteins and DNA. Endogenous free radical scavengers such as glutathione and the polyamines (e.g, spermidine and spermine) can inhibit the action of ROS. In particular, heme oxygenase-1 (HO-1), the enzyme involved in heme protein metabolism, can provide antioxidant protection through the production of the antioxidant bilirubin. Furthermore, polyamines have been shown to indirectly increase HO-1 content and antioxidant protection. The beta2-adrenoceptor agonist clenbuterol has been shown to stimulate polyamine synthesis and by extension, might provide a margin of antioxidant protection through increasing HO-1 content. However, it is unclear whether the polyamines are acting as a tertiary messengers for antioxidant protection in the be beta2-adrenoceptor signal transduction pathway. The purpose of this study was to study the role of the polyamine pathway in attenuating free radical-induced damage.

Growth and Morphogenesis of Embryonic Mouse Organs on Non-Coated and Extracellular Matrix-Coated Biopore Membrane: (organ-culture/growth/morphogenesis/extracellular matrix/Biopore).

Embryonic mouse salivary glands, pancreata, and kidneys were isolated from embryos of appropriate gestational age by microdissection, and were cultured on Biopore membrane either non-coated or coated with type I collagen or Matrigel. As expected, use of Biopore membrane allowed high quality photomicroscopy of the living organs. In all organs extensive mesenchymal spreading was observed in the presence of type I collagen or Matrigel. However, differences were noted in the effects of extracellular matrix (ECM) coatings on epithelial growth and morphogenesis: salivary glands were minimally affected, pancreas morphogenesis was adversely affected, and kidney growth and branching apparently was enhanced. It is suggested that these differences in behaviour reflect differences in the strength of interactions between the mesenchymal cells and their surrounding endogenous matrix, compared to the exogenous ECM macromolecules. This method will be useful for culture of these and other embryonic organs. In particular, culture of kidney rudiments on ECM-coated Biopore offers a great improvement over previously used methods which do not allow morphogenesis to be followed in vitro.

Anatomy as the backbone of an integrated first year medical curriculum: design and implementation.

Morehouse School of Medicine chose to restructure its first year medical curriculum in 2005. The anatomy faculty had prior experience in integrating courses, stemming from the successful integration of individual anatomical sciences courses into a single course called Human Morphology. The integration process was expanded to include the other first year basic science courses (Biochemistry, Physiology, and Neurobiology) as we progressed toward an integrated curriculum. A team, consisting of the course directors, a curriculum coordinator, and the Associate Dean for Educational and Faculty Affairs, was assembled to build the new curriculum. For the initial phase, the original course titles were retained but the lecture order was reorganized around the Human Morphology topic sequence. The material from all four courses was organized into four sequential units. Other curricular changes included placing laboratories and lectures more consistently in the daily routine, reducing lecture time from 120 to 90 minute blocks, eliminating unnecessary duplication of content, and increasing the amount of independent study time. Examinations were constructed to include questions from all courses on a single test, reducing the number of examination days in each block from three to one. The entire restructuring process took two years to complete, and the revised curriculum was implemented for the students entering in 2007. The outcomes of the restructured curriculum include a reduction in the number of contact hours by 28%, higher or equivalent subject examination average scores, enhanced student satisfaction, and a first year curriculum team better prepared to move forward with future integration.