Unilateral heat accelerates bone elongation and lengthens extremities of growing mice.

Linear growth failure results from a broad spectrum of systemic and local disorders that can generate chronic musculoskeletal disability. Current bone lengthening protocols involve invasive surgeries or drug regimens, which are only partially effective. Exposure to warm ambient temperature during growth increases limb length, suggesting that targeted heat could noninvasively enhance bone elongation. We tested the hypothesis that daily heat exposure on one side of the body unilaterally increases femoral and tibial lengths. Mice (N = 20) were treated with 40 °C unilateral heat for 40 min/day for 14 days post-weaning. Non-treated mice (N = 6) served as controls. Unilateral increases in ear (8.8%), hindfoot (3.5%), femoral (1.3%), and tibial (1.5%) lengths were obtained. Tibial elongation rate was > 12% greater (15 µm/day) on the heat-treated side. Extremity lengthening correlated with temperature during treatment. Body mass and humeral length were unaffected. To test whether differences persisted in adults, mice were examined 7-weeks post-treatment. Ear area, hindfoot, femoral, and tibial lengths were still significantly increased ∼6%, 3.5%, 1%, and 1%, respectively, on the heat-treated side. Left-right differences were absent in non-treated controls, ruling out inherent side asymmetry. This model is important for designing noninvasive heat-based therapies to potentially combat a range of debilitating growth impediments in children.

Independent learning modules enhance student performance and understanding of anatomy.

Didactic lessons are only one part of the multimodal teaching strategies used in gross anatomy courses today. Increased emphasis is placed on providing more opportunities for students to develop lifelong learning and critical thinking skills during medical training. In a pilot program designed to promote more engaged and independent learning in anatomy, self-study modules were introduced to supplement human gross anatomy instruction at Joan C. Edwards School of Medicine at Marshall University. Modules use three-dimensional constructs to help students understand complex anatomical regions. Resources are self-contained in portable bins and are accessible at any time. Students use modules individually or in groups in a structured self-study format that augments material presented in lecture and laboratory. Pilot outcome data, measured by feedback surveys and examination performance statistics, suggest that the activity may be improving learning in gross anatomy. Positive feedback on both pre- and post-examination surveys showed that students felt the activity helped to increase their understanding of the topic. In concordance with student perception, average examination scores on module-related laboratory and lecture questions were higher in the two years of the pilot program compared with the year before its initiation. Modules can be fabricated on a modest budget using minimal resources, making implementation practical for smaller institutions. Upper level medical students assist in module design and upkeep, enabling continuous opportunities for vertical integration across the curriculum. This resource offers a feasible mechanism for enhancing independent and lifelong learning competencies, which could be a valuable complement to any gross anatomy curriculum.

Hindlimb heating increases vascular access of large molecules to murine tibial growth plates measured by in vivo multiphoton imaging.

Advances in understanding the molecular regulation of longitudinal growth have led to development of novel drug therapies for growth plate disorders. Despite progress, a major unmet challenge is delivering therapeutic agents to avascular-cartilage plates. Dense extracellular matrix and lack of penetrating blood vessels create a semipermeable "barrier," which hinders molecular transport at the vascular-cartilage interface. To overcome this obstacle, we used a hindlimb heating model to manipulate bone circulation in 5-wk-old female mice (n = 22). Temperatures represented a physiological range of normal human knee joints. We used in vivo multiphoton microscopy to quantify temperature-enhanced delivery of large molecules into tibial growth plates. We tested the hypothesis that increasing hindlimb temperature from 22°C to 34°C increases vascular access of large systemic molecules, modeled using 10, 40, and 70 kDa dextrans that approximate sizes of physiological regulators. Vascular access was quantified by vessel diameter, velocity, and dextran leakage from subperichondrial plexus vessels and accumulation in growth plate cartilage. Growth plate entry of 10 kDa dextrans increased >150% at 34°C. Entry of 40 and 70 kDa dextrans increased <50%, suggesting a size-dependent temperature enhancement. Total dextran levels in the plexus increased at 34°C, but relative leakage out of vessels was not temperature dependent. Blood velocity and vessel diameter increased 118% and 31%, respectively, at 34°C. These results demonstrate that heat enhances vascular carrying capacity and bioavailability of large molecules around growth plates, suggesting that temperature could be a noninvasive strategy for modulating delivery of therapeutics to impaired growth plates of children.