Citations

Introduction Female distance runners are at elevated risk for impaired bone remodeling due to high mechanical loading, potential low energy availability, and sustained inflammatory stress. Collagen peptide (CP) supplementation has been proposed as a nutritional strategy to support type I collagen synthesis and modulate osteoimmune signaling; however, evidence in premenopausal endurance athletes is limited. This pilot randomized, double-blind, placebo-controlled trial examined the effects of four weeks of high-dose CP supplementation on markers of bone metabolism and inflammatory activity in endurance-trained premenopausal women. Methods Twenty-two participants (18–35 years; ≥35 miles/week [>56km/week]) were randomized to CP (INT; 20 g/day) or isocaloric maltodextrin (CON). Pre- and post-intervention assessments, conducted in the early follicular phase, included serum procollagen type I N-terminal propeptide (P1NP), plasma C-terminal telopeptide of type I collagen (CTX-1), serum soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG), the sRANKL/OPG ratio, and interleukin-6 (IL-6). Repeated-measures ANCOVAs were performed, adjusting for accumulated running distance and vitamin D status. Results A significant group × time interaction was observed for P1NP ( p = 0.04), with increases in INT and no change in CON. No significant interaction was observed for CTX-1 ( p = 0.13). Significant interactions were also observed for sRANKL ( p = 0.046) and IL-6 ( p = 0.03). No significant interaction effects were detected for sRANKL, OPG, or the sRANKL/OPG ratio. Discussion Short-term CP supplementation increased a marker of bone formation, altered osteoclast-related signaling, and reduced IL-6 in endurance-trained premenopausal women. These findings support the potential for CP-mediated modulation of bone turnover and inflammatory activity and warrant further investigation in larger, adequately powered trials incorporating structural bone outcomes.

OBJECTIVES We aimed to characterize the frequency of major complications of acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) and adolescents present at 6 months after initial presentation. METHODS The Pediatric Research Immune Network on SARS-CoV-2 and MIS-C (PRISM) study was a prospective cohort at 20 US pediatric academic medical centers. Individuals aged younger than 21 years meeting any of the following were enrolled: SARS-CoV-2 detection within 7 days, Centers for Disease Control and Prevention (CDC) MIS-C criteria, or CDC MIS-C criteria except having involvement of 1 organ system. The study was designed to assess the proportion of children with major complications (cardiovascular, pulmonary, gastrointestinal/hepatic, renal, and/or neurologic) 6 months after presentation. RESULTS Data were analyzed on 229 hospitalized participants: 59 with COVID-19 (mean age 10.4 years; SD, 5.5) and 170 with MIS-C (mean age 10.1 years; SD, 4.8). Overall, 42.8% were female, making up 55.9% and 38.2% of the COVID-19 and MIS-C groups, respectively. Overall, the frequencies of major complications at 6 months after initial presentation were: 16/195 (8.2%) cardiovascular, 11/154 (7.1%) pulmonary, 11/154 (7.1%) gastrointestinal/hepatic, 3/152 (2.0%) renal, and 3/189 (1.6%) neurologic. Organ system complications did not differ significantly between the COVID-19 and MIS-C groups. Six of 14 (42.9%) COVID-19 and 21/26 (80.7%) MIS-C participants with at least 1 six-month complication had no underlying medical condition that may have been associated with their complication(s). CONCLUSIONS Major complications were infrequent but observed in children without underlying medical conditions, underscoring the importance of prospective follow-up to optimize management and elucidate the complications associated with severe SARS-CoV-2 infection in children.

BACKGROUND AND OBJECTIVES: Craniopharyngiomas are complex intracranial tumors that pose significant challenges in surgical management. We aimed to develop risk-stratified surgical outcome benchmarks for adult patients undergoing endoscopic craniopharyngioma resection by using the Registry of Adenomas of the Pituitary and Related Disorders database to facilitate comparisons across institutions and guide clinical decision-making. METHODS: A retrospective cohort of adult patients (18 years and older) with craniopharyngioma undergoing a first-time endoscopic transnasal surgery across 14 academic centers in the United States was analyzed using data collected from 2011 to 2024. Patients were stratified into low-risk and high-risk cohorts based on criteria including age, body mass index, selected tumor characteristics (size, infundibular relationship, intraventricular extension), and previous radiation. Surgical outcomes were analyzed, and benchmarking ranges were defined using the established methodology. RESULTS: The overall cohort included 318 patients with a mean age of 50 years. Upon benchmarking analysis (50th-75th percentile performance), low-risk patients (n = 136) had a median length of stay of 4.0 to 6.0 days, 90-day readmission rates of 15.5% to 22.2%, skilled nursing facility discharge rates of <1.0%, postoperative cerebrospinal fluid leak incidence of <1.0% to 14.3%, gross total resection rates of 50.0% to 60.8%, new postoperative arginine vasopressin deficiency rates of 33.3% to 50.0%, and tumor progression/recurrence rates of <1.0% to 18.3% over a median follow-up period of 27.0 (IQR 10.5-56.5) months. Benchmarking ranges were proposed for each outcome to facilitate cross-institutional comparisons. CONCLUSION: Establishing surgical outcome benchmarks for adult patients undergoing craniopharyngioma resection using data from the Registry of Adenomas of the Pituitary and Related Disorders provides a framework for assessing surgical performance and guiding clinical decision-making. Benchmark ranges can inform institutional quality improvement efforts, perioperative risk stratification, and patient counseling regarding expected postoperative outcomes.

Abstract The impact of microglia antigen presentation on CNS infiltrating CD8 T cells responses during neurotropic virus infection has been difficult to define. Using Theiler’s murine encephalomyelitis virus (TMEV) infection of neurons as a model system, our laboratory has previously determined that H-2D b restricted, but not H-2K b restricted CD8 T cells are required for viral clearance, demonstrating the role of discrete MHC class I alleles. To determine the extent microglia antigen presentation impacts brain-infiltrating CD8 T cells, our laboratory generated novel single MHC class I conditional knockout mice in which H-2K b or H-2D b can be specifically deactivated in TMEM119+ microglia with tamoxifen administration. During TMEV infection, conditional knockout of H-2K b in microglia reduced antigen-specific CD8 T cell proliferation in the brain. Meanwhile, mice with deletion of D b in microglia had reduced levels of perforin in antigen-specific CD8 T cells. Furthermore, microglia specific deletion of H-2D b reduced CD8 T cell numbers in the brain and preserved blood-brain barrier (BBB) integrity. Microglial D b restricted antigen presentation was also essential for the reactivation of CD8 tissue resident memory (TRM) cells and BBB integrity during memory recall responses. These findings further our understanding of how brain infiltrating antiviral CD8 T cell responses are impacted by microglia, as well as define how this cellular interaction contributes to BBB disruption during neuroinflammation. These findings also have high significance to our understanding of how microglia impact CD8 TRM cell populations that reside in the brain long after virus infection is cleared. Graphical abstract

Weight loss and thermogenic dietary supplements often claim to promote weight loss by increasing metabolic activity. This study characterized the identity and quantity of common supplement ingredients. Commercially available products (n=98) whose name, label, or packaging referenced promotion of thermogenesis or weight loss were identified at retail outlets or web search. Product ingredients were divided into 6 possible categories of ingredient quantity based on packaging. Extracts included raw plant ingredients, plant extracts, etc. Small molecule isolates included caffeine, melatonin, etc. The remaining 4 ingredient categories were lipids, minerals, vitamins, and amino acids. Product suggested serving size was 13±16 grams (40±71 Cal). Green tea (521±1334 mg), cayenne (57±46 mg) and black pepper (5±2 mg) extracts were the most common, with 22 ingredients of 137 extracts being quantified 3 or more times. Caffeine (181±59 mg), acetyl-L-carnitine (595±368 mg) and L-carnitine (510±345 mg) were the most common small molecule isolates, with 11 of 49 total ingredients quantified in at least 3 products. There were 18 different lipid or fatty acid ingredients with only linoleic (740±718 mg) and lipoic (250±235 mg) acids being quantified in at least 3 products. Chromium (268±282 µg), calcium (156±110 mg), and iodine (145±85 mg) were the most common minerals, with 10 of 14 minerals quantified in at least 3 products. Cobalamin (49±78 µg), pyridoxine (8±9 mg) and folate (391±252 mcg) were the 3 most common vitamins, with 5 of 13 vitamins quantified in at least 3 products. Alanine (2133±924 mg), tryptophan (60±40 mg) and tyrosine (250±229 mg) were the most common amino acids, with 3 of 9 amino acids quantified in at least 3 products. Ingredients were indicated as “present” but not quantified 541 times across the 98 products. Proprietary formulas and vaguely worded ingredients were listed in 44 of the 98 products. The 98 thermogenic and weight loss products contained a tremendous variety of ingredients, although only 53 of the 240 different ingredients were present in 3 or more products. Variable ingredient content and quantity, complicate blanket claims about function, efficacy, or safety. Future evaluations of ingredient contents should determine if specific amounts confer discernable benefits. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: Hypoxia challenges the regulation of arterial oxygenation (SaO 2 ), eliciting a compensatory increase in ventilation ([Formula: see text]E) to preserve blood-gas homeostasis. However, the ability to maintain blood-gas homeostasis during hypoxic exercise may differ between sexes due to differences in chemoreflex drive and the mechanical capacity to augment ventilation. The purpose of this study was to evaluate sex differences in ventilatory and blood-gas responses to progressive hypoxia during moderate walking exercise. Specifically, we asked whether females would be more susceptible to hypoxemia. We hypothesized that females would exhibit a smaller ventilatory response and a less steep ventilatory CO 2 -response (Δ[Formula: see text]E/ΔPaCO 2 ) compared with males, resulting in a greater reduction in SaO 2 during progressive hypoxia. Methods: Twenty-six physically active adults (15M: age 35.3±9.4; [Formula: see text]O 2 max 54.3±15.5 mL/kg/min, 11F: age 36.2±9.0; [Formula: see text]O 2 max 44.6±5.2 mL/kg/min) were studies during two visits. Visit 1: we determined the participants’ maximal oxygen uptake ([Formula: see text]O 2 max) during an incremental treadmill test. Visit 2: participants walked at ~50% of their [Formula: see text]O 2 max while we reduced the fraction of inspired oxygen (FiO 2 ) progressively every 5 minutes (0.21, 0.19, 0.17, 0.15, 0.13, 0.12, 0.11). Arterial blood samples were collected from a brachial artery catheter during the final 30 seconds of each stage; cardiometabolic and ventilatory data were averaged over the final minute of each stage. The test ended when peripheral oxygen saturation (SpO 2 ) fell below 70%. Because 0.13 FiO 2 was the lowest stage completed by all participants, Δ responses were calculated from 0.21 to 0.13 FiO 2 . Independent t-tests compared Δ responses between sexes; data are mean±SD, significance was set at p < 0.05. Results: There was no significant difference in ΔSaO 2 between sexes across hypoxia (M: −22.0±3.7%; F: −22.8±5.5%; p = 0.89). Males had higher arterial oxygen content (CaO 2 ) than females across all stages (M: 20.6±1.2 to 16.0±1.4 mL O 2 ·dL -1 ; F: 18.5±1.1 to 13.8±2.0 mL O 2 ·dL -1 ), but the ΔCaO 2 during hypoxia was not significantly different between sexes (M: −4.6±0.7; F: −4.7±1.4 mL O 2 ·dL -1 ; p = 0.86). Similarly, there was no significant difference in the change in arterial CO 2 (ΔPaCO 2 ) between sexes (M: −5.8±1.5 mmHg; F: −6.5±3.6 mmHg, p = 0.51). In contrast, males exhibited a significantly greater increase in ventilation (Δ[Formula: see text]E: +13.9±4.2 L·min -1 ) than females (+8.6±2.7 L·min -1 ; p = 0.003). Consequently, the ventilatory CO 2 -response (Δ[Formula: see text]E/ΔPaCO 2 ) was steeper in males (−2.46±0.66 L·min -1 ·mmHg -1 ) compared with females (−1.57±0.68 L·min -1 ·mmHg -1 ; p = 0.004). However, when Δ[Formula: see text]E was expressed relative to maximal ventilatory capacity (%[Formula: see text]Emax), there was no sex difference (M: 8.8±2.6% vs F: 8.3±2.8%; p = 0.68). Conclusion: Females were not more susceptible to hypoxemia than males; both sexes showed comparable reductions in SaO 2 during moderate exercise in progressive hypoxia. Reductions in PaCO 2 were also similar, indicating comparable ventilatory drive. Although males exhibited a larger absolute increase in [Formula: see text]E and a steeper ventilatory CO 2 -response, this difference disappeared when Δ[Formula: see text]E was expressed relative to %[Formula: see text]Emax. These findings indicate that apparent sex differences in ventilation during hypoxia largely reflect differences in ventilatory capacity rather than true differences in oxygenation or ventilatory drive. Taken together, these findings challenge the assumption that females are inherently more susceptible to hypoxemia or have a lower ventilatory drive than males during moderate hypoxic exercise. Funding: NIH T32 DK007352, UL1 TR002377 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: During hypoxic exercise, oxygen transport becomes increasingly challenged as oxygen availability decreases. As the inspired oxygen fraction (FiO 2 ) decreases, peripheral oxygen saturation (SpO 2 ) gradually declines, then drops rapidly upon reaching the steepest point of the sigmoidal shaped, oxyhemoglobin dissociation curve. This reduction in FiO 2 creates a distinct SpO 2 “breakpoint,” which likely represents the threshold at which compensatory mechanisms, such as increases in ventilation and cardiac output, can no longer maintain arterial oxygenation. Several physiological factors may modulate this breakpoint, including hemoglobin concentration, blood volume, and ventilatory capacity. This study aimed to determine the SpO 2 breakpoint during steady-state, submaximal, hypoxic exercise and examine whether factors like sex, age, and fitness level influence the SpO 2 breakpoint. We hypothesized that SpO 2 breakpoints would differ by sex, age, and fitness level, with earlier breakpoints visible in females, older adults, and those with higher aerobic fitness. Methods: Twenty-six physically active adults (15M: age 35±9 yrs, [Formula: see text]O 2 max 54.3±15.5 mL/kg/min, 11F: age 38±10 yrs, [Formula: see text]O 2 max 44.6±5.2 mL/kg/min) participated in a two-day study. Day one: participants performed a treadmill [Formula: see text]O 2 max test. Day two: participants walked at a steady state of ~50% of their [Formula: see text]O 2 max, for 40 minutes, while FiO 2 was progressively reduced every 5 minutes in a stepwise fashion (0.25, 0.21, 0.19, 0.17, 0.15, 0.13, 0.12, 0.11). The test was terminated when SpO 2 dropped below 70%. SpO 2 was measured continuously using a clinical-grade oximeter. Analysis was performed in RStudio by first determining each participant’s individual SpO 2 vs time breakpoint. Male and Female breakpoints were compared to assess sex-based differences. To evaluate whether SpO 2 breakpoint timing differed by age or fitness level, participants were then divided into tertiles for each variable. Age tertiles were derived from the sample distribution of chronological age, and fitness tertiles were defined using [Formula: see text]O 2 max (L/min). Mean breakpoint times were compared between the highest and lowest tertiles for both age and fitness. Mean SpO 2 breakpoints were compared between groups using independent sample t-tests. Significance was set to p< 0.05. Results: The overall mean breakpoint occurred at an SpO 2 of 90.7±2.8% during the 0.17 FiO 2 stage. No significant sex differences were observed in breakpoint SpO 2 and timing (M: SpO 2 = 90.7±2.7%, time = 18.6 min; F: SpO 2 = 90.7±3.0%, time = 17.7 min; p = 0.961). Age did not significantly influence breakpoint (younger tertile [21-30 yrs] SpO 2 = 91.0±2.4%, time = 18.4 min; older tertile [41-60 yrs] SpO 2 = 91.1±2.4%, time = 17.2 min, p = 0.953). Additionally, fitness level showed no significant difference on breakpoint (low fitness [1.91-3.01 L/min]: SpO 2 = 90.3±3.1%, time = 17.8 min; high fitness [4.38-5.25 L/min]: SpO 2 = 90.4±2.9%, time = 19.2 min; p = 0.992). Conclusion: During a hypoxic, steady state walking exercise, at ~50% [Formula: see text]O 2 max, we observed no difference in the peripheral oxygen saturation breakpoint, across sex, age, and fitness level. This may suggest that moderate exercise in hypoxia does not sufficiently challenge the cardiopulmonary system for individual variations in oxygen transport to influence the breakpoint. These findings imply that the SpO 2 breakpoint, during hypoxic exercise, may represent a physiological marker of the upper limit for maintaining oxygen saturation in healthy adults. Applying this protocol to identify SpO 2 breakpoints may offer insights for improving pharmacological interventions and our understanding of clinical populations with impaired oxygen transport. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Color Doppler twinkling is associated with rough-surfaced objects like kidney stones, some clinical breast biopsy markers, and polymethyl methacrylate (PMMA) bone cement. Microbubbles are theorized as the predominant source of twinkling, supported by decreased twinkling under increased pressure. PMMA, metallic breast markers, a low-twinkling PMMA sample, and a non-twinkling metal rod were scanned in a pressure chamber up to 1000 psi using a General Electric Logiq E9 system and C1-6 probe (1.7–3.6 MHz Doppler transmit frequency). Clinical markers maintained distinct twinkling up to 250 psi. PMMA often twinkled at higher pressures, sometimes up to 1000 psi. The controls showed no twinkling. To understand physical structure associations with twinkling, the samples were scanned in a micro-CT system with a pixel resolution of 2 μm. Analysis of PMMA and Cork internal voids showed no correlation with twinkling. However, a correlation between Sa (average difference between the mean surface profile and actual surface profile) values and twinkling was found. This indicates that internal structure is not important for twinkling, and certain surface roughness is critical, possibly providing sites for surface microbubbles to oscillate from incident ultrasound waves.

Cancer-induced muscle wasting affects many people with cancer, reducing treatment tolerance and survival. We identified a natural dietary compound, ursolic acid, that attenuates muscle atrophy across five preclinical cancer models spanning pancreatic, colon, and lung cancer. Ursolic acid inhibits cancer-induced changes in muscle mRNA expression, preserves muscle strength, and remains protective during chemotherapy, without affecting food intake or tumor burden. These results identify ursolic acid as a promising, translatable dietary supplement for supportive cancer care.