Selection of endurance capabilities and the trade-off between pressure and volume in the evolution of the human heart.

Chimpanzees and gorillas, when not inactive, engage primarily in short bursts of resistance physical activity (RPA), such as climbing and fighting, that creates pressure stress on the cardiovascular system. In contrast, to initially hunt and gather and later to farm, it is thought that preindustrial human survival was dependent on lifelong moderate-intensity endurance physical activity (EPA), which creates a cardiovascular volume stress. Although derived musculoskeletal and thermoregulatory adaptations for EPA in humans have been documented, it is unknown if selection acted similarly on the heart. To test this hypothesis, we compared left ventricular (LV) structure and function across semiwild sanctuary chimpanzees, gorillas, and a sample of humans exposed to markedly different physical activity patterns. We show the human LV possesses derived features that help augment cardiac output (CO) thereby enabling EPA. However, the human LV also demonstrates phenotypic plasticity and, hence, variability, across a wide range of habitual physical activity. We show that the human LV's propensity to remodel differentially in response to chronic pressure or volume stimuli associated with intense RPA and EPA as well as physical inactivity represents an evolutionary trade-off with potential implications for contemporary cardiovascular health. Specifically, the human LV trades off pressure adaptations for volume capabilities and converges on a chimpanzee-like phenotype in response to physical inactivity or sustained pressure loading. Consequently, the derived LV and lifelong low blood pressure (BP) appear to be partly sustained by regular moderate-intensity EPA whose decline in postindustrial societies likely contributes to the modern epidemic of hypertensive heart disease.

Perioperative Antibiotic Prophylaxis: Single and 24-Hour Antibiotic Dosages are Equally Effective at Preventing Periprosthetic Joint Infection in Total Joint Arthroplasty.

BACKGROUND: Perioperative antibiotic prophylaxis is used to prevent surgical site infection and periprosthetic joint infection (PJI) after total joint arthroplasty (TJA). Secondary to a national shortage of cefazolin, patients at our institution began receiving a single preoperative prophylactic antibiotic dose for primary TJA and no 24-hour postoperative antibiotic prophylaxis. The purpose of the study was to compare the efficacy of single-dose antibiotic use versus 24-hour dosing of prophylactic antibiotics in the prevention of acute PJI and short-term complications after primary TJA. METHODS: A retrospective review of 3317 patients undergoing primary TJA performed from January 2015 to December 2019 identified 554 patients who received a single dose of preoperative antibiotic prophylaxis during the antibiotic shortage and 2763 patients who received post-TJA 24-hour antibiotic prophylaxis before the shortage. Patient records were evaluated for acute PJI, superficial infection, 90-day reoperation, and 90-day complications. RESULTS: There were no significant differences in patient characteristics between single-dose and 24-hour antibiotic groups. Similarly, there were no significant differences in rates of acute PJI (0.7% vs 0.2%; P = .301), superficial infection (2.4% vs 1.4%; P = .221), 90-day reoperation (2.1% vs 1.1%; P = .155), and 90-day complications (9.9% vs 7.9%; P = .169) between single and 24-hour antibiotic dose. Post hoc power analysis demonstrated adequate sample size, beta = 93%. CONCLUSION: Single-dose prophylactic antibiotics did not lead to an increased risk of acute PJI or short-term complications after TJA. Our study suggests that administration of a single antibiotic dose may be safely considered in patients undergoing routine primary TJA.

Specific circulating microRNAs display dose-dependent responses to variable intensity and duration of endurance exercise.

Circulating microRNAs (c-miRNAs), plasma-based noncoding RNAs that control posttranscriptional gene expression, mediate processes that underlie phenotypical plasticity to exercise. The relationship and biological relevance between c-miRNA expression and variable dose exercise exposure remains uncertain. We hypothesized that certain c-miRNAs respond to changes in exercise intensity and/or duration in a dose-dependent fashion. Muscle release of such c-miRNAs may then deplete intracellular stores, thus facilitating gene reprogramming and exercise adaptation. To address these hypotheses, healthy men participated in variable intensity ( n = 12, 30 × 1 min at 6, 7, and 8 miles/h, order randomized) and variable duration ( n = 14, 7 × 1 mile/h for 30, 60, and 90 min, order randomized) treadmill-running protocols. Muscle-enriched c-miRNAs (i.e., miRNA-1 and miRNA-133a) and others with known relevance to exercise were measured before and after exercise. c-miRNA responses followed three profiles: 1) nonresponsive (miRNA-21 and miRNA-210), 2) responsive to exercise at some threshold but without dose dependence (miRNA-24 and miRNA-146a), and 3) responsive to exercise with dose dependence to increasing intensity (miRNA-1) or duration (miRNA-133a and miRNA-222). We also studied aerobic exercise-trained mice, comparing control, low-intensity (0.5 km/h), or high-intensity (1 km/h) treadmill-running protocols over 4 wk. In high- but not low-intensity-trained mice, we found increased plasma c-miR-133a along with decreased intracellular miRNA-133a and increased serum response factor, a known miR-133a target gene, in muscle. Characterization of c-miRNAs that are dose responsive to exercise in humans and mice supports the notion that they directly mediate physiological adaptation to exercise, potentially through depletion of intracellular stores of muscle-specific miRNAs. NEW & NOTEWORTHY In this study of humans and mice, we define circulating microRNAs in plasma that are dose responsive to exercise. Our data support the notion that these microRNAs mediate physiological adaptation to exercise potentially through depletion of intracellular stores of muscle-specific microRNAs and releasing their inhibitory effects on target gene expression.

Stem Cells and Acellular Preparations in Bone Regeneration/Fracture Healing: Current Therapies and Future Directions.

Bone/fracture healing is a complex process with different steps and four basic tissue layers being affected: cortical bone, periosteum, fascial tissue surrounding the fracture, and bone marrow. Stem cells and their derivatives, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, hematopoietic stem cells, skeletal stem cells, and multipotent stem cells, can function to artificially introduce highly regenerative cells into decrepit biological tissues and augment the healing process at the tissue level. Stem cells are molecularly and functionally indistinguishable from standard human tissues. The widespread appeal of stem cell therapy lies in its potential benefits as a therapeutic technology that, if harnessed, can be applied in clinical settings. This review aims to establish the molecular pathophysiology of bone healing and the current stem cell interventions that disrupt or augment the bone healing process and, finally, considers the future direction/therapeutic options related to stem cells and bone healing.

Bony Decompression of a Chronically Painful Intercostal Nerve Yields Immediate and Long-Lasting Pain Relief: A Case Report.

CASE: The case of an active 16-year-old adolescent girl who presented with rib malunion and 1 year of unremitting intercostal nerve pain after sustaining multiple rib fractures is presented. She underwent successful bony and soft-tissue decompression of her eighth and ninth intercostal nerves to relieve neurogenic symptoms. CONCLUSION: When conservative treatment fails, chronic intercostal nerve pain due to chest wall trauma may be effectively managed with surgical bony decompression of the offending intercostal bundle(s). Anatomic knowledge of the intercostal nerve and a critical history and physical examination were critical for accurate diagnosis and surgical decompression of the patient's intercostal nerve.

Self-Inflicted Hand Amputation without Replantation in a Patient with Body Integrity Identity Disorder: A Case Report.

CASE: We describe a patient who self-amputated his hand using a log splitter, because of a long-standing belief that the limb "did not belong to him." On admission, he refused replantation and was found to be nonpsychotic. He was diagnosed with body integrity identity disorder (BIID) and declared competent to make his own medical decisions. A revision amputation was performed. CONCLUSION: BIID is a challenging diagnosis that physicians treating traumatic injuries should be aware of. Many ethicists support elective amputation as a definitive treatment, because of potential harm reduction and because BIID does not respond to conservative modalities such as pharmacotherapy.

Cardiovascular response to prescribed detraining among recreational athletes.

Exercise-induced cardiac remodeling (EICR) and the attendant myocardial adaptations characteristic of the athlete's heart may regress during periods of exercise reduction or abstinence. The time course and mechanisms underlying this reverse remodeling, specifically the impact of concomitant plasma volume (PV) contraction on cardiac chamber size, remain incompletely understood. We therefore studied recreational runners ( n = 21, age 34 ± 7 yr; 48% male) who completed an 18-wk training program (~7 h/wk) culminating in the 2016 Boston Marathon after which total exercise exposure was confined to <2 h/wk (no single session >1 h) for 8 wk. Cardiac structure and function, exercise capacity, and PV were assessed at peak fitness (10-14 days before) and at 4 wk and 8 wk postmarathon. Mixed linear modeling adjusting for age, sex, V̇o2peak, and marathon finish time was used to compare data across time points. Physiological detraining was evidenced by serial reductions in treadmill performance. Two distinct phases of myocardial remodeling and hematological adaptation were observed. After 4 wk of detraining, there were significant reductions in PV (Δ -6.0%, P < 0.01), left ventricular (LV) wall thickness (Δ -8.1%, <0.05), LV mass (Δ -10.3%, P < 0.001), and right atrial area (Δ -8.2%, P < 0.001). After 8 wk of detraining, there was a significant reduction in right ventricle chamber size (end-diastolic area Δ = -8.0%, P < 0.05) without further concomitant reductions in PV or LV wall thickness. Abrupt reductions in exercise training stimulus result in a structure-specific time course of reverse cardiac remodeling that occurs largely independently of PV contraction. NEW & NOTEWORTHY Significant reverse cardiac remodeling, previously documented among competitive athletes, extends to recreational runners and occurs with a distinct time course. Initial reductions in plasma volume and left ventricular (LV) mass, driven by reductions in wall thickness, are followed by contraction of the right ventricle. Consistent with data from competitive athletes, LV chamber volumes appear less responsive to detraining and may be a more permanent adaptation to sport.