Bone healing complications such as delayed healing or non-union affect 5-10 % of patients with a long-bone fracture and lead to reduced quality of life and increased health-care costs. The gut microbiota and the metabolites they produce, mainly short-chain fatty acids (SCFAs), have been shown to impact nearly all organs of the human body including bone. SCFAs show broad activity in positively influencing bone healing outcomes either by acting directly on cell types involved in fracture healing, such as osteoblasts, osteoclasts, chondrocytes and fibroblasts, or indirectly, by shaping an appropriate anti-inflammatory and immune regulatory response. Due to the ability of SCFAs to influence osteoblast and osteoclast differentiation, SCFAs may also affect the integration of orthopaedic implants in bone. In addition, SCFA-derivatives have already been used in a variety of tissue engineering constructs to reduce inflammation and induce bone tissue production. The present review summarises the current knowledge on the role of the gut microbiota, in particular through the action of SCFAs, in the individual stages of bone healing and provides insights into how SCFAs may be utilised in a manner beneficial for fracture healing and surgical reconstruction.

Short-chain fatty acids (SCFAs) produced by the gut microbiota have previously been demonstrated to play a role in numerous chronic inflammatory diseases and to be key mediators in the gut-bone signaling axis. However, the role of SCFAs in bone fracture healing and its impact on systemic inflammation during the regeneration process has not been extensively investigated yet. The aim of this study was to first determine the effects of the SCFA butyrate on key cells involved in fracture healing in vitro, namely, osteoclasts and mesenchymal stromal cells (MSCs), and second, to assess if butyrate supplementation or antibiotic therapy impacts bone healing, systemic immune status, and inflammation levels in a murine osteotomy model. Butyrate significantly reduced osteoclast formation and resorption activity in a dose-dependent manner and displayed a trend for increased calcium deposits in MSC cultures. Numerous genes associated with osteoclast differentiation were differentially expressed in osteoclast precursor cells upon butyrate exposure. In vivo, antibiotic-treated mice showed reduced SCFA levels in the cecum, as well as a distinct gut microbiome composition. Furthermore, circulating proinflammatory TNFα, IL-17a, and IL-17f levels, and bone preserving osteoprotegerin (OPG), were increased in antibiotic-treated mice compared to controls. Antibiotic-treated mice also displayed a trend towards delayed bone healing as revealed by reduced mineral apposition at the defect site and higher circulating levels of the bone turnover marker PINP. Butyrate supplementation resulted in a lower abundance of monocyte/macrophages in the bone marrow, as well as reduced circulating proinflammatory IL-6 levels compared to antibiotic- and control-treated mice. In conclusion, this study supports our hypothesis that SCFAs, in particular butyrate, are important contributors to successful bone healing by modulating key cells involved in fracture healing as well as systemic inflammation and immune responses.

Objective To determine readability, understandability, and actionability of online health information related to transgender voice care. Study Design Review of online materials. Setting Academic medical center. Methods A Google search of “transgender voice care” was performed with the first 50 websites meeting inclusion criteria included. Readability was assessed using the Flesch Reading Ease Score (FRES), Flesch-Kincaid Grade Level (FKGL), and the Simple Measure of Gobbledygook (SMOG). Understandability and actionability were measured by 2 independent reviewers using the Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P). Unpaired t tests were used to compare clinician- and patient-oriented sites, surgical and nonsurgical sites, and sites that discuss nonbinary indications for voice care. Analysis of variance was used to compare sites that discuss voice feminization, masculinization, both, or neither. Results Average scores across the cohort for FRES, FKGL, and SMOG were 43.77 ± 13.52, 12.14 ± 2.66, and 11.30 ± 1.93, respectively, indicating materials were above a 12th-grade reading level. PEMAT-P scores for understandability and actionability were 64.95% ± 15.78% and 40.55% ± 23.86%, respectively. Patient-oriented sites were significantly more understandable and actionable than clinician-oriented sites ( P < .02). Websites that discussed only voice feminization were significantly more readable according to objective metrics (FKGL, SMOG) than websites that discussed both feminization and masculinization or those that did not differentiate care types ( P < .05). Conclusion Online information written about transgender voice care is written at a level above what is recommended for patient education materials. Providers may improve accessibility of transgender voice care by enhancing readability of online materials.

Background: Functional lower extremity reconstruction primarily aims to restore independent ambulation. We sought to define the synergies recruited during a walking gait to inform donor selection for various motor deficits. With these findings, we discuss the functional neuromuscular components of independent gait with the goal of informing lower extremity reconstruction. Methods: A systematic review was performed using MEDLINE for articles published between January 2000 and December 2020. Search terms included (1) “motor module(s),” “synergy,” “motor pattern,” or “motor primitive” and (2) “gait,” “walking,” “ambulation,” or “locomotion.” Abstracts/full texts were reviewed by two independent reviewers. Results: A total of 38 studies were selected. The average reported number of synergies and variance accounted for was 4.5 ± 0.9 and 88.6% ± 7.7%, respectively. Four motor modules were conserved across nearly all studies. Conclusions: Walking can be reduced to the sequential activation of four motor modules. Activities during the stance phase are critical for both standing stability and forward progression and should be prioritized for reconstruction with the goal of preserving efficient gait. Muscles recruited during swing, except those used for ankle dorsiflexion, are less prone to injury and benefit from greater redundancy, less often necessitating reconstruction. With the emphasis on stability during stance, several synergistic or sometimes even antagonistic tendons can be used to replace their counterparts and restore efficient, independent ambulation. With a finite supply of donor tissues, and in the absence of well-defined clinical outcomes data, this research allows us to effectively prioritize reconstructive goals and maximize patient outcomes.