Hydraulic permeability and compressive properties of porcine and human synovium.

The synovium is a multilayer connective tissue separating the intra-articular spaces of the diarthrodial joint from the extra-synovial vascular and lymphatic supply. Synovium regulates drug transport into and out of the joint, yet its material properties remain poorly characterized. Here, we measured the compressive properties (aggregate modulus, Young's modulus, and Poisson's ratio) and hydraulic permeability of synovium with a combined experimental-computational approach. A compressive aggregate modulus and Young's modulus for the solid phase of synovium were quantified from linear regression of the equilibrium confined and unconfined compressive stress upon strain, respectively (HA = 4.3 ± 2.0 kPa, Es = 2.1 ± 0.75, porcine; HA = 3.1 ± 2.0 kPa, Es = 2.8 ± 1.7, human). Poisson's ratio was estimated to be 0.39 and 0.40 for porcine and human tissue, respectively, from moduli values in a Monte Carlo simulation. To calculate hydraulic permeability, a biphasic finite element model's predictions were numerically matched to experimental data for the time-varying ramp and hold phase of a single increment of applied strain (k = 7.4 ± 4.1 × 10-15 m4/N.s, porcine; k = 7.4 ± 4.3 × 10-15 m4/N.s, human). We can use these newly measured properties to predict fluid flow gradients across the tissue in response to previously reported intra-articular pressures. These values for material constants are to our knowledge the first available measurements in synovium that are necessary to better understand drug transport in both healthy and pathological joints.

Action learning and public health pedagogy: Student reflections from an experiential public health course.

Introduction: Applied practice experiences are essential components of the Masters of Public Health (MPH) curriculum. The objective of this study was to examine students' perspectives on the skills and expertise they developed in an MPH course offering applied practice opportunities. Methods: Of 236 students who took the course from 2008 to 2018, email addresses were obtained for 212 and 104 completed the consent form. Following consent, reflection essays were de-identified and analyzed using a rapid qualitative analysis approach. The essays addressed students' learning experiences and application of the competencies for MPH programs set by the Council for Education in Public Health (CEPH). Deductive and inductive analytical lenses were used to identify the key lessons learned by each cohort of students. Semi-structured guides and matrixes for essay analysis were created using assignment instructions and CEPH competencies. Results: Although the reflection paper assignment varied across the years, commonalities were observed in the student reflections. Key themes included turning theory into practice, navigating the complex environment of public health practice, skill building, critical self-reflection, challenges encountered, and elements that facilitated project success. Students reported developing practical skills, such as planning for independent research (e.g., preparing for institutional review board (IRB) submission, consulting with faculty and other experts), identifying realistic approaches for data extraction during chart reviews and analyses of electronic medical records, and disseminating findings for diverse stakeholders and audiences. Students also reported strengthening cross-cutting skills such as communication, teamwork, and problem-solving that were useful for navigating power dynamics and balancing competing interests and expectations. Students explored their identity as public health professionals as they navigated the dynamics of public health practice. Conclusion: The applied practice experience served as a valuable tool for knowledge and skills acquisition. Moreover, it served as an opportunity for students to engage with the unique organizational cultures of their respective community partners and to deepen their understanding the complexities of conducting meaningful community-engaged research. Implications: This study demonstrates the utility of analyzing students' critical self-reflections as a tool for exploring learning experiences when training future public health professionals. The findings can help educators design future applied practice experiences.

A mechanism for the activation of the mechanosensitive Piezo1 channel by the small molecule Yoda1.

Mechanosensitive Piezo1 and Piezo2 channels transduce various forms of mechanical forces into cellular signals that play vital roles in many important biological processes in vertebrate organisms. Besides mechanical forces, Piezo1 is selectively activated by micromolar concentrations of the small molecule Yoda1 through an unknown mechanism. Here, using a combination of all-atom molecular dynamics simulations, calcium imaging and electrophysiology, we identify an allosteric Yoda1 binding pocket located in the putative mechanosensory domain, approximately 40 Å away from the central pore. Our simulations further indicate that the presence of the agonist correlates with increased tension-induced motions of the Yoda1-bound subunit. Our results suggest a model wherein Yoda1 acts as a molecular wedge, facilitating force-induced conformational changes, effectively lowering the channel's mechanical threshold for activation. The identification of an allosteric agonist binding site in Piezo1 channels will pave the way for the rational design of future Piezo modulators with clinical value.