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We investigated the interaction between angiogenic and osteogenic factors in bone formation and bone healing with ex vivo gene therapy using muscle-derived stem cells genetically engineered to express human bone morphogenetic protein-4 (BMP4), VEGF, or VEGF-specific antagonist (soluble Flt1). Our results show that although VEGF alone did not improve bone regeneration, it acted synergistically with BMP4 to increase recruitment of mesenchymal stem cells, to enhance cell survival, and to augment cartilage formation in the early stages of endochondral bone formation. These early effects, coupled with accelerated cartilage resorption, eventually led to a significant enhancement of bone formation and bone healing. The beneficial effect of VEGF on bone healing elicited by BMP4 depends critically on the ratio of VEGF to BMP4, with an improper ratio leading to detrimental effects on bone healing. Finally, we show that soluble Flt1 inhibits bone formation elicited by BMP4. Thus, VEGF plays an important role in bone formation elicited by BMP4, and it can significantly enhance BMP4-elicited bone formation and regeneration through multiple mechanisms. This study has important implications for the formulation of new strategies to improve bone healing through increasing mesenchymal stem cell recruitment and survival, in combination with muscle-derived stem cell-based gene therapy.

\"Includes a 6-week total-body workout program.\"

Recent advances in molecular biology have led the way for novel approaches to improve bone healing. The ideal growth factor, vector, and delivery systems for producing bone in an immune competent animal model, however, have yet to be identified. Using a retrovirus encoding BMP4 and recently isolated muscle-derived stem cells (MDSCs), we demonstrated the following: MDSCs undergo osteogenic differentiation in response to BMP4 in a dose-dependent manner; retrovirus encoding BMP4 can efficiently transduce MDSCs, both enhancing osteogenic differentiation and inhibiting myogenic differentiation; transduced MDSCs can produce high levels of functional BMP4 as they differentiate toward an osteogenic lineage; allogeneic transduced MDSCs can induce robust de novo bone formation in immunocompetent mice despite the presence of an immune reaction, demonstrating the ability of this retroviral-BMP4-muscle construct to provide sufficient stimuli for osteoinduction in vivo; MDSCs appear to deliver BMP4, respond to the human BMP4 in an autocrine manner, and actively participate in bone formation, thus serving both osteoinductive and osteoproductive roles; and the BMP4-expressing MDSCs can induce bone formation and improve bone healing in a critical-sized skull defect in immunocompetent mice. Therefore, we believe that technology based on the MDSCs and vector system has great potential for promoting bone healing in a variety of musculoskeletal conditions.

Graphic novels and comics can be difficult to catalog due to the graphic and textual nature of the medium. The most popular and used formats for comics and graphic novels would not met the standard for most institutions, but since there are a number of digital files already available in the Comic book RAR (CBR) and Comic Book Zip(CBZ) reader file format with little to no metadata attached those files should be cataloged using either a known xml or other schema and then have a crosswalk applied to them to adapt them to the more controlled, and more complex, Comic Book Markup Language (CBML) that should be used by information institutions. CBML is based in Text Encoding Initiative (TEI), while the standard for comic books as it can be added to XML such as Dublin Core, and is extremely involved and far more complicated than the average institution will need. The project purposed is a set of records created using specific standard for metadata cataloging of comics and graphic novels, CBR and CBZ reader files, in Dublin Core (DC) with a detailed crosswalk to the more Advanced Comic Book Format with the CBML in the appropriate sections.

Background Hormone Replacement Therapy (HRT) is considered the gold standard for management of vasomotor symptoms. It can also help improve bone health, potentially reducing the risk of osteoporosis and fractures. There is current debate regarding the use of HRT and its risk-to-benefit ratio for cardiovascular and cognitive health. While there is a plethora of research reporting HRT use among the general population, research on HRT use among resistance-trained women is lacking. In the United States, HRT use among the general population of post-menopausal women has rapidly declined. It was estimated to be 4.7% in 2020, down from 26.9% in 1999. The purpose of this study was to survey HRT usage among post-menopausal resistance-trained women.Methods The present study is part of a larger overall female fitness menopause survey consisting of 132 questions that were developed collaboratively by the authors and conducted through Qualtrics Software (Qualtrics, Provo, UT, USA). The survey was distributed via online platforms and relied on voluntary participation, which may have limited the respondent pool to individuals with internet access and higher digital literacy. This preliminary descriptive analysis focused on the question: “Are you currently using HRT?” with three close-ended responses: “Yes”; “No”; “I prefer not to answer.” In the survey, HRT use was defined as taking estrogen or progesterone. Data is presented descriptively.Results A total of 943 subjects identified themselves as post-menopausal. Of these, 514 reported to be currently using HRT (55% of total respondents).Conclusion This study suggests, within the population of self-identified post-menopausal resistance-trained women, there may be a much larger rate of HRT usage than previously reported. One notable limitation of this study is the use of a survey disseminated through social media platforms. This approach introduces potential selection bias, as users of social media platforms may not reflect the broader population in terms of socioeconomic status, education, and other demographic or behavioral characteristics. Additionally, the voluntary nature of survey participation on social media may lead to self-selection bias, whereby individuals with strong opinions or vested interest in the topic are more likely to respond. As such, the sample may over-represent particular demographic groups or viewpoints, limiting the generalizability of the findings. Future research should consider using stratified sampling or supplementing online recruitment with offline methods to ensure broader representation.

Background: Concussions make up a significant proportion of sports injuries. This study aimed to describe the mechanisms of injury and associated symptoms of pediatric patients diagnosed with concussions (age range, 4-17 years) from contact sports. Hypothesis: Mechanisms of injury would differ based on sex and age, with female athletes and younger athletes aged 4 to 11 years sustaining fewer concussions from player-to-player contact. Study Design: Descriptive epidemiology study. Methods: The National Electronic Injury Surveillance System was queried for all contact sport concussions presented to United States emergency departments. The sports analyzed included basketball, football, soccer, hockey, rugby, and lacrosse. Descriptive data, mechanisms of injury, and associated symptoms were analyzed for each sport. Differences in the number of concussions sustained by year and sport, the severity of the injury, and associated symptoms were compared using chi-square test, and differences in proportion were calculated for mechanisms of injury stratified by sex and age. Results: A total of 12,602 youth athletes sustained concussions between 2012 and 2021. Most patients were male (78.5%), with a mean age of 13.48 years. Football concussions were the most common, with 45.32% of the concussions. The mechanism of injury was largely sport-specific, with player-to-player contact the most common overall. Older male athletes were more likely to have concussions from player-to-player contact, whereas younger athletes were more impacted by head-to-ground mechanisms. Symptom presentation was not sport-specific, and headache and dizziness were the most common presentation at 41.2% and 26.2%, respectively. Conclusion: The most important overall mechanism of injury was player-to-player contact, especially in older male youth athletes, whereas younger athletes were more likely to be concussed due to head-to-ground injuries.

We investigated the interaction between angiogenic and osteogenic factors in bone formation and bone healing with ex vivo gene therapy using muscle-derived stem cells genetically engineered to express human bone morphogenetic protein-4 (BMP4), VEGF, or VEGF-specific antagonist (soluble Flt1). Our results show that although VEGF alone did not improve bone regeneration, it acted synergistically with BMP4 to increase recruitment of mesenchymal stem cells, to enhance cell survival, and to augment cartilage formation in the early stages of endochondral bone formation. These early effects, coupled with accelerated cartilage resorption, eventually led to a significant enhancement of bone formation and bone healing. The beneficial effect of VEGF on bone healing elicited by BMP4 depends critically on the ratio of VEGF to BMP4, with an improper ratio leading to detrimental effects on bone healing. Finally, we show that soluble Flt1 inhibits bone formation elicited by BMP4. Thus, VEGF plays an important role in bone formation elicited by BMP4, and it can significantly enhance BMP4-elicited bone formation and regeneration through multiple mechanisms. This study has important implications for the formulation of new strategies to improve bone healing through increasing mesenchymal stem cell recruitment and survival, in combination with muscle-derived stem cell-based gene therapy.