Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RA) and fibroblast growth factor-21 (FGF21) confer similar metabolic benefits. GLP-1RA induce FGF21, leading us to investigate mechanisms engaged by the GLP-1RA liraglutide to increase FGF21 levels and the metabolic relevance of liraglutide-induced FGF21. Circulating FGF21 levels were measured in fasted male C57BL/6J, neuronal GLP-1R knockout, β-cell GLP-1R knockout, and liver peroxisome proliferator-activated receptor alpha knockout mice treated acutely with liraglutide. To test the metabolic relevance of liver FGF21 in response to liraglutide, chow-fed control and liver Fgf21 knockout (Liv^Fgf21−/−) mice were treated with vehicle or liraglutide in metabolic chambers. Body weight and composition, food intake, and energy expenditure were measured. Since FGF21 reduces carbohydrate intake, we measured body weight in mice fed matched diets with low- (LC) or high-carbohydrate (HC) content and in mice fed a high-fat, high-sugar (HFHS) diet. This was done in control and Liv^Fgf21−/− mice and in mice lacking neuronal β-klotho (Klb) expression to disrupt brain FGF21 signaling. Liraglutide increases FGF21 levels independently of decreased food intake via neuronal GLP-1R activation. Lack of liver Fgf21 expression confers resistance to liraglutide-induced weight loss due to attenuated reduction of food intake in chow-fed mice. Liraglutide-induced weight loss was impaired in Liv^Fgf21−/− mice when fed HC and HFHS diets but not when fed a LC diet. Loss of neuronal Klb also attenuated liraglutide-induced weight loss in mice fed HC or HFHS diets. Our findings support a novel role for a GLP-1R-FGF21 axis in regulating body weight in a dietary carbohydrate-dependent manner.

Background: Fibrous dysplasia (FD) is often difficult for skull base surgeons to address. FD arises due to the abnormal proliferation of fibroblasts, ultimately resulting in immature osseous tissue replacing normal cancellous bone. When the skull base is involved, it can result in cranial nerve compression. FD affecting the optic canal and optic nerve is the most concerning as new onset of vision loss is considered a surgical emergency. The prevalence of FD is approximately 3.6 per 1,000,000. The most severe implications of this disease are neurological deficits due to cranial nerve compression, cosmetic appearance, and high recurrence rates even in the setting of surgical and medical therapy interventions. Methods: A PubMed search of “pediatric fibrous dysplasia management” using MESH Terms was conducted. Articles were excluded for non-English languages, inaccessibility, and events/erratum/letters to the editor. Included articles were in English, as well as encompassed pediatric FD case reports or comprehensive reviews of FD that discussed pediatric presentations. Results: A total of 109 articles were reviewed, and 44 were included in the final review. Most articles were case reports. There is a clear need for guidelines regarding surgical intervention, especially in the pediatric population, where hormonal fluctuation can influence rates of recurrence and bony deformity. Overall, most surgeons recommend close observation with biomarkers and radiographic imaging for asymptomatic patients until at least the age of 16 years old. Conservative methods, such as RANK-L inhibitors, can be utilized to decrease growth with some success, especially in older adolescents. Conclusion: This review is an update on this disease and its presentations, imaging findings, and treatment options. The current literature lacks clear guidance on management, especially in regard to surgical intervention or recurrence monitoring algorithms.

Females are uniquely sensitive to drugs of abuse at specific points in their reproductive cycle. Females' endogenous opioid system contributes to both reward-related processes and maternally relevant physiological functions, yet less is known about how adolescent opioid exposure impacts females' future behavior, ranging from parental caregiving to opioid preference. The present study explores 2 questions: (a) are there sex differences in response to adolescent oxycodone exposure, spontaneous withdrawal, and oxycodone preference in adulthood, and (b) to what extent does this pregestational opioid exposure alter females' future maternal caregiving behavior? Female and male mice received 12d of oxycodone or saline injections during mid/late adolescence, and drug was then withheld. Some females were then mated and experienced a drug-free pregnancy. Following parturition, females' maternal behavior and motivation were assessed. All mice then underwent a place conditioning procedure to assess the incentive value of oxycodone during adulthood. Mice displayed similar behavioral responses to oxycodone (e.g., sensitization) and patterns of withdrawal behaviors, independent of sex. Mice showed strong group preferences for the oxycodone-paired chamber, and the strength of these preferences did not differ by sex or maternal status. Postpartum females' maternal behavior and motivation were also similar despite adolescent drug history. Together, results did not suggest overt sex differences in response to adolescent oxycodone exposure and that, in females, a range of motivated behaviors may be relatively resilient to such perturbations during adolescence. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: Orthopaedic sports medicine is among the most popular subspecialties. Understanding the trends in sports medicine research over time can offer insight into progress and innovation within the field. The purpose of this study was to assess both the quality of the current literature and trends in gender diversity and inclusion by evaluating publishing characteristics of sports medicine studies in The Journal of Bone and Joint Surgery-American Volume (JBJS-A) from 2007 to 2021. Methods: Sports medicine studies in JBJS-A from 2007 to 2021 were identified using JBJS subspeciality tags for “sports medicine” articles and organized by study type, number of authors, sex of the authors, academic degree(s) of the first and last authors, level of evidence, country of publication, citations, and use of patient-reported outcomes (PROM). Results: A total of 784 studies were reviewed, and 513 met inclusion criteria. Clinical therapeutic studies were the most common publication (48%). There was an increase in the publication of clinical prognostic studies (17%-25%, p = 0.037) and a significant increase in the use of PROM measures over time (13%-47%, p < 0.001). The total number of authors increased over the study period (4.8-6.3), but there was no significant increase in female authorship. Only 15% of the 784 studies included a female author, with an average of 0.8 female authors per article (range 0-8) compared with 4.6 males (range 1-14). Conclusion: The significant increase in the use of PROMs in sports medicine studies indicates that the quality of research has improved over the 15-year period. The gender disparity in authorship has remained stagnant. Only 11% of all first authors and 9% of senior authors were female. The number of included international studies improved over time; however, the United States remains the most prolific publisher. Despite these areas of growth, this study suggests that there is room for improvement of authorship gender diversity in orthopaedic sports medicine research. Level of Evidence: Level III. See Instructions for Authors for a complete description of levels of evidence.