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Discusses self-learning exercises (SLEs) incorporated into the Medical Physiology course for first-year students at the Morehouse School of Medicine in Atlanta, GA. Twenty to thirty percent of course material is presented in these exercises instead of in lectures. The exercises develop active learning and problem-solving skills. Formal analysis showed that SLEs did not significantly impair learning. (Author/AIM)

Self-learning exercises (SLE) are used to supplement student education on year one of the Medical Physiology course at Morehouse School of Medicine. SLE programs were reviewed and modified following a twelve-month trial period to enhance learning strategy at the school. Examples of the material used in SLE are given. SLE material at the school does not include multiple-choice questions.

Rotator cuff supraspinatus tendon injuries are common with high rates of anatomic failure after surgical repair. The purpose of the study was to define clinically relevant features of a mouse model of supraspinatus tendon injury to determine painful, functional, and structural outcomes; we further investigated two cell populations mediating healing using genetic lineage tracing after full detachment and repair of the supraspinatus tendon in mice. The pain was assessed using the mouse grimace scale and function by gait analysis and tensile testing. Histological and microCT analyses were used to determine enthesis/tendon and bone structure, respectively. Lineage tracing was carried out using inducible Cre lines for ScxCreERT2 (tendon cells) and αSMACreERT2 (myofibroblasts and mesenchymal progenitors). Mice only expressed pain transiently after surgery despite long‐term impairment of functional and structural properties. Gait, tensile mechanical properties, and bone properties were significantly reduced after injury and repair. Lineage tracing showed relatively few Scxlin tendon cells while αSMAlin cells contributed strongly to scar formation. Despite surgical reattachment of healthy tendon, lineage tracing revealed poor preservation of supraspinatus tendon after acute injury and loss of tendon structure, suggesting that tendon degeneration is also a key impediment of successful rotator cuff repair. Scar formation after surgery is mediated largely by αSMAlin cells and results in permanently reduced functional and structural properties. [ABSTRACT FROM AUTHOR]

A coronary blood flow (CBF) fluctuation pattern during sleep which has not been previously observed in sleep research is reported. The observation was obtained in sleep studies using dogs and involved episodes of pause in heart rhythm lasting from 1.1-8.0 seconds. These pauses occurred primarily during the transition from slow-wave sleep to other sleep stages, and was followed by CBF increases ranging up to 84% and averaging 30%. The surge in CBF was attributed to enhanced vagal activity, although further research is suggested to confirm this.

In this review, we highlight themes from a recent workshop focused on "Plasticity of Cell Fate in Musculoskeletal Tissues" held at the Orthopaedic Research Society's 2019 annual meeting. Experts in the field provided examples of mesenchymal cell plasticity during normal musculoskeletal development, regeneration, and disease. A thorough understanding of the biology underpinning mesenchymal cell plasticity may offer a roadmap for promoting regeneration while attenuating pathologic differentiation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:708‐718, 2020 [ABSTRACT FROM AUTHOR]

Tendons are connective tissues with limited healing potential which results in permanently impaired function. Although direct mechanical testing of tendon remains the gold standard for functional analyses, this assay is terminal and tracking healing over time requires the use of many animals. An alternative method for quantifying tendon function is gait analysis, which is non-terminal and enables longitudinal tracking of the same animal. To date, commercial systems used to analyze gait are mostly applied to study neurobehavior, and applications for tendon research has been limited. Since these systems typically output many parameters, it is challenging to know which parameter is most relevant for a specific injury model. To address this challenge, we used a well-established rodent locomotion system (CatWalk XT) to measure longitudinal gait parameters in sham and Achilles tendon-injured mice (from PREOP to 56 days post-injury) and identified relevant and reproducible parameters specifically associated with Achilles tendon injury and healing. Micro computed tomography (micro- CT) and mechanical testing also confirmed persistent tendon impairment in the same animals at the terminal timepoint. Collectively, our results provide a useful reference and recommendation of CatWalk gait parameters and the control comparisons that both conserve the use of animals while maintaining high reproducibility standards for Achilles tendon injury studies. [ABSTRACT FROM AUTHOR]

Tendon and ligament injuries are a leading cause of healthcare visits with significant impact in terms of economic cost and reduced quality of life. To date, reparative strategies remain largely restricted to conservative treatment or surgical repair. However, these therapies fail to restore native tendon structure and function; thus, the tissue may re‐rupture or degenerate with time. To improve tendon healing, one promising strategy may be harnessing the innate potential of resident tendon stem/progenitor cells (TSPCs) to guide tenogenic regeneration. In this review, we outline recent advances in the identification and characterization of putative TSPC populations, and discuss biochemical, biomechanical, and biomaterial methods employed for their culture and differentiation. Finally, we identify limitations in our current understanding of TSPC biology, key challenges for their use, and potential therapeutic strategies to inform cell‐based tendon repair. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1270–1280, 2019. [ABSTRACT FROM AUTHOR]

Despite considerable efforts to develop cellular, molecular, and structural repair strategies and restore intervertebral disk function after injury, the basic biology underlying intervertebral disk healing remains poorly understood. Remarkably, little is known about the origins of cell populations residing within the annulus fibrosus, or their phenotypes, heterogeneity, and roles during healing. This review focuses on recent literature highlighting the intrinsic and extrinsic cell types of the annulus fibrosus in the context of the injury and healing environment. Spatial, morphological, functional, and transcriptional signatures of annulus fibrosus cells are reviewed, including inner and outer annulus fibrosus cells, which we propose to be referred to as annulocytes. The annulus also contains peripheral cells, interlamellar cells, and potential resident stem/progenitor cells, as well as macrophages, T lymphocytes, and mast cells following injury. Phases of annulus fibrosus healing include inflammation and recruitment of immune cells, cell proliferation, granulation tissue formation, and matrix remodeling. However, annulus fibrosus healing commonly involves limited remodeling, with granulation tissues remaining, and the development of chronic inflammatory states. Identifying annulus fibrosus cell phenotypes during health, injury, and degeneration will inform reparative regeneration strategies aimed at improving annulus fibrosus healing. [ABSTRACT FROM AUTHOR]

The rotator cuff is composed of several distinct muscles and tendons that function in concert to coordinate shoulder motion. Injuries to these tendons frequently result in permanent dysfunction and persistent pain. Despite considerable advances in operation techniques, surgical repair alone still does not fully restore rotator cuff function. This review focuses on recent research in the use of biologics and stem cell‐based therapies to augment repair, highlighting promising avenues for future work and remaining challenges. While a number of animal models are used for rotator cuff studies, the anatomy of the rotator cuff varies dramatically between species. Since the rodent rotator cuff shares the most anatomical features with the human, this review will focus primarily on rodent models to enable consistent interpretation of outcome measures. [ABSTRACT FROM AUTHOR]

Tissue engineering is a promising approach for the repair of articular cartilage defects, with engineered constructs emerging that match native tissue properties. However, the inflammatory environment of the damaged joint might compromise outcomes, and this may be impacted by the choice of cell source in terms of their ability to operate anabolically in an inflamed environment. Here, we compared the response of engineered cartilage derived from native chondrocytes and mesenchymal stem cells (MSCs) to challenge by TNFα and IL‐1β in order to determine if either cell type possessed an inherent advantage. Compositional (extracellular matrix) and functional (mechanical) characteristics, as well as the release of catabolic mediators (matrix metalloproteinases [MMPs], nitric oxide [NO]) were assessed to determine cell‐ and tissue‐level changes following exposure to IL‐1β or TNF‐α. Results demonstrated that MSC‐derived constructs were more sensitive to inflammatory mediators than chondrocyte‐derived constructs, exhibiting a greater loss of proteoglycans and functional properties at lower cytokine concentrations. While MSCs and chondrocytes both have the capacity to form functional engineered cartilage in vitro, this study suggests that the presence of an inflammatory environment is more likely to impair the in vivo success of MSC‐derived cartilage repair. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2901–2910, 2018. [ABSTRACT FROM AUTHOR]

Butler, Karyn L., Alice H. Huang, and Judith K. Gwathmey. [AT.sub.1]-receptor blockade enhances ischemic preconditioning in hypertrophied rat myocardium. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H2482-H2487, 1999.--The purpose of this study was to determine whether ischemic preconditioning protects contractile function in hypertrophied rat myocardium from ischemia-reperfusion (UR) injury. Male salt-sensitive rats were fed a high-salt diet for 2 wk to induce myocardial hypertrophy. Nonhypertrophied hearts were obtained from age-matched Sprague-Dawley (SD) rats fed a regular diet. Heart weight-to-body weight ratios were higher in salt-sensitive rats than in SD rats (6.9 [+ or -] 0.2 vs. 4.7 [+ or -] 0.2 g/kg, P [is less than] 0.01). A second group of salt-sensitive and SD rats was administered losartan (10 mg [multiplied by] [kg.sup.-1] [multiplied by] [day.sup.-1]), an [AT.sub.1]-receptor blocker, for 1 wk before the study. Isolated hearts were preconditioned with transient ischemia before global I/R. After I/R, preconditioned hypertrophied hearts exhibited greater recovery of left ventricular developed pressure compared with that of preconditioned normal hearts (73 [+ or -] 8 vs. 18 [+ or -] 8%, P [is less than] 0.01). Left ventricular developed pressure was further enhanced by losartan in both hypertrophied and normal myocardium (99 [+ or -] 5 vs. 73 [+ or -] 8%, P [is less than] 0.05 and 97 [+ or -] 15 vs. 18 [+ or -] 8%, P [is less than] 0.01). Hypertrophied rat myocardium can be protected from UR-induced contractile dysfunction by ischemic preconditioning. Losartan improves the ischemic tolerance of normal and hypertrophied myocardium. angiotensin II receptors; cardiac preconditioning; myocardial hypertrophy