Fifty-one percent of humans are born with ovaries. As the ovarian production of estrogen diminishes in midlife and ultimately stops, it is estimated that more than 47 million women worldwide enter the menopause transition annually. More than 70% will experience musculoskeletal symptoms and 25% will be disabled by them through the transition from perimenopause to postmenopause. This often-unrecognized collective of musculoskeletal symptoms, largely influenced by estrogen flux, includes arthralgia, loss of muscle mass, loss of bone density and progression of osteoarthritis, among others. In isolation, it can be difficult for clinicians and patients to adequately appreciate the substantial role of decreasing estrogen, anticipate the onset of related symptoms and actively treat to mitigate future detrimental processes. Thus, in this review we introduce a new term, the musculoskeletal syndrome of menopause, to describe the collective musculoskeletal signs and symptoms associated with the loss of estrogen. Given the significant effects of these processes on quality of life and the associated personal and financial costs, it is important for clinicians and the women they care for to be aware of this terminology and the constellation of musculoskeletal processes for which proper risk assessment and prophylactic management are of consequence.

The human skeleton is a metabolically active system that is constantly regenerating via the tightly regulated and highly coordinated processes of bone resorption and formation. Emerging evidence reveals fascinating new insights into the role of sphingolipids, including sphingomyelin, sphingosine, ceramide, and sphingosine-1-phosphate, in bone homeostasis. Sphingolipids are a major class of highly bioactive lipids able to activate distinct protein targets including, lipases, phosphatases, and kinases, thereby conferring distinct cellular functions beyond energy metabolism. Lipids are known to contribute to the progression of chronic inflammation, and notably, an increase in bone marrow adiposity parallel to elevated bone loss is observed in most pathological bone conditions, including aging, rheumatoid arthritis, osteoarthritis, and osteomyelitis. Of the numerous classes of lipids that form, sphingolipids are considered among the most deleterious. This review highlights the important primary role of sphingolipids in bone homeostasis and how dysregulation of these bioactive metabolites appears central to many chronic bone-related diseases. Further, their contribution to the invasion, virulence, and colonization of both viral and bacterial host cell infections is also discussed. Many unmet clinical needs remain, and data to date suggest the future use of sphingolipid-targeted therapy to regulate bone dysfunction due to a variety of diseases or infection are highly promising. However, deciphering the biochemical and molecular mechanisms of this diverse and extremely complex sphingolipidome, both in terms of bone health and disease, is considered the next frontier in the field.

Cord blood (CB) mononuclear cells (MNC) are being tested in clinical trials to treat hypoxic-ischemic (HI) brain injuries. Although early results are encouraging, mechanisms underlying potential clinical benefits are not well understood. To explore these mechanisms further, we exposed mouse brain organotypic slice cultures to oxygen and glucose deprivation (OGD) and then treated the brain slices with cells from CB or adult peripheral blood (PB). We found that CB-MNCs protect neurons from OGD-induced death and reduced both microglial and astrocyte activation. PB-MNC failed to affect either outcome. The protective activities were largely mediated by factors secreted by CB-MNC, as direct cell-to-cell contact between the injured brain slices and CB cells was not essential. To determine if a specific subpopulation of CB-MNC are responsible for these protective activities, we depleted CB-MNC of various cell types and found that only removal of CB CD14⁺ monocytes abolished neuroprotection. We also used positively selected subpopulations of CB-MNC and PB-MNC in this assay and demonstrated that purified CB-CD14⁺ cells, but not CB-PB CD14⁺ cells, efficiently protected neuronal cells from death and reduced glial activation following OGD. Gene expression microarray analysis demonstrated that compared to PB-CD14⁺ monocytes, CB-CD14⁺ monocytes over-expressed several secreted proteins with potential to protect neurons. Differential expression of five candidate effector molecules, chitinase 3-like protein-1, inhibin-A, interleukin-10, matrix metalloproteinase-9 and thrombospondin-1, were confirmed by western blotting, and immunofluorescence. These findings suggest that CD14⁺ monocytes are a critical cell-type when treating HI with CB-MNC.

As both the proportion of older people and the length of life increases globally, a rise in age-related degenerative diseases, disability, and prolonged dependency is projected. However, more sophisticated biomedical materials, as well as an improved understanding of human disease, is forecast to revolutionize the diagnosis and treatment of conditions ranging from osteoarthritis to Alzheimer’s disease as well as impact disease prevention. Another, albeit quieter, revolution is also taking place within society: human augmentation. In this context, humans seek to improve themselves, metamorphosing through self-discipline or more recently, through use of emerging medical technologies, with the goal of transcending aging and mortality. In this review, and in the pursuit of improved medical care following aging, disease, disability, or injury, we first highlight cutting-edge and emerging materials-based neuroprosthetic technologies designed to restore limb or organ function. We highlight the potential for these technologies to be utilized to augment human performance beyond the range of natural performance. We discuss and explore the growing social movement of human augmentation and the idea that it is possible and desirable to use emerging technologies to push the boundaries of what it means to be a healthy human into the realm of superhuman performance and intelligence. This potential future capability is contrasted with limitations in the right-to-repair legislation, which may create challenges for patients. Now is the time for continued discussion of the ethical strategies for research, implementation, and long-term device sustainability or repair.

Background: Advances in artificial intelligence (AI), machine learning, and publicly accessible language model tools such as ChatGPT‐3.5 continue to shape the landscape of modern medicine and patient education. ChatGPT’s open access (OA), instant, human‐sounding interface capable of carrying discussion on myriad topics makes it a potentially useful resource for patients seeking medical advice. As it pertains to orthopedic surgery, ChatGPT may become a source to answer common preoperative questions regarding total knee arthroplasty (TKA) and total hip arthroplasty (THA). Since ChatGPT can utilize the peer‐reviewed literature to source its responses, this study seeks to characterize the validity of its responses to common TKA and THA questions and characterize the peer‐reviewed literature that it uses to formulate its responses. Methods: Preoperative TKA and THA questions were formulated by fellowship‐trained adult reconstruction surgeons based on common questions posed by patients in the clinical setting. Questions were inputted into ChatGPT with the initial request of using solely the peer‐reviewed literature to generate its responses. The validity of each response was rated on a Likert scale by the fellowship‐trained surgeons, and the sources utilized were characterized in terms of accuracy of comparison to existing publications, publication date, study design, level of evidence, journal of publication, journal impact factor based on the clarivate analytics factor tool, journal OA status, and whether the journal is based in the United States. Results: A total of 109 sources were cited by ChatGPT in its answers to 17 questions regarding TKA procedures and 16 THA procedures. Thirty‐nine sources (36%) were deemed accurate or able to be directly traced to an existing publication. Of these, seven (18%) were identified as duplicates, yielding a total of 32 unique sources that were identified as accurate and further characterized. The most common characteristics of these sources included dates of publication between 2011 and 2015 (10), publication in The Journal of Bone and Joint Surgery (13), journal impact factors between 5.1 and 10.0 (17), internationally based journals (17), and journals that are not OA (28). The most common study designs were retrospective cohort studies and case series (seven each). The level of evidence was broadly distributed between Levels I, III, and IV (seven each). The averages for the Likert scales for medical accuracy and completeness were 4.4/6 and 1.92/3, respectively. Conclusions: Investigation into ChatGPT’s response quality and use of peer‐reviewed sources when prompted with archetypal pre‐TKA and pre‐THA questions found ChatGPT to provide mostly reliable responses based on fellowship‐trained orthopedic surgeon review of 4.4/6 for accuracy and 1.92/3 for completeness despite a 64.22% rate of citing inaccurate references. This study suggests that until ChatGPT is proven to be a reliable source of valid information and references, patients must exercise extreme caution in directing their pre‐TKA and THA questions to this medium.