Citations

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.

Purpose: The study compares refractive outcomes of secondary intraocular lens (SIOL) surgery performed by vitreoretinal, anterior segment, and both surgeons. Methods: Eyes included in this study underwent SIOL surgery from 2012 to 2024 and had a final postoperative visual acuity of 20/50 or better. Regression analysis compared refractive outcomes, and chi-squared analysis compared complications between subspecialty of SIOL surgeons. Results: A total of 94, 104, and 80 eyes were included in the retina surgeon, anterior segment surgeon, and combo surgeon cohorts, respectively. There was no significant difference in error between target and final postoperative spherical equivalence between retina and combo ( P = 0.079), retina and anterior segment ( P = 0.135), or anterior segment and combo cohorts ( P = 0.567). There was no significant difference in number of eyes with final spherical equivalence within 1 diopter of target spherical equivalence between retina and combo ( P = 0.136), retina and anterior segment ( P = 0.061), or anterior segment and combo cohorts ( P = 0.783). The retina cohort had higher postoperative corneal edema than the combo ( P = 0.017) and the anterior segment cohorts ( P = 0.035). The combo cohort had more postoperative retinal detachment than the anterior segment cohort ( P = 0.046). Conclusion: In eyes with good final vision, retina and anterior segment surgeons have similar refractive outcomes after SIOL surgery.

Abstract Introduction Ultrasonic vaping devices like SURGE are marketed as safer alternatives to conventional coil-based electronic cigarettes like JUUL due to their lower operating temperatures. However, their impact on cardiovascular health has not been fully characterized. Methods Sprague–Dawley rats were exposed daily for 9 weeks to aerosol generated from SURGE, JUUL, or clean air. Heart rate variability was continuously monitored via implanted telemetry. Cardiac fibrosis was quantified using histological analysis. Temperature profiles of SURGE, JUUL, and Nautilus (a coil-based tank device) were recorded. Aerosol samples were analyzed for carbonyl compounds using high-performance liquid chromatography. Results Both SURGE and JUUL exposures significantly reduced heart rate variability (high frequency and total power) compared with air. JUUL exposure significantly increased cardiac fibrosis; SURGE showed a similar mean fibrosis level but greater variability, resulting in a non-significant difference. SURGE devices operated at lower peak temperatures (~131°C) than JUUL (~239°C) and Nautilus (~160–170°C). Despite having the lowest temperature, SURGE emitted higher levels of carbonyl compounds than JUUL, although still substantially lower than Nautilus. Conclusions Although SURGE operates without coils and at lower temperatures than coiled vaping devices, it generates higher levels of carbonyls than some coiled devices and impairs cardiac autonomic regulation, and it can cause cardiac fibrosis comparable with JUUL although with high variability; that is, SURGE does not reliably avoid the increase in fibrosis caused by conventional electronic cigarettes. These findings suggest that non-thermal mechanisms predominate in mediating cardiovascular toxicity associated with ultrasonic vaping, challenging the assumption that coil-free designs are inherently safer. Implications Despite its lower operating temperature and coil-free design, the SURGE ultrasonic vaping device impaired cardiac autonomic function and promoted fibrosis at a mean level comparable to that of JUUL. These findings challenge claims of reduced harm from coil-less vaping technologies and suggest that non-thermal mechanisms may drive toxicity. Regulatory evaluations should consider device emissions and physiological outcomes—not just hardware features. Physicians and policymakers should be aware that coil-less systems may still pose cardiovascular risks, and marketing these devices as inherently safer may mislead users and undermine tobacco harm reduction efforts.

Chylous effusion is a complication most frequently seen in the iatrogenic setting secondary to thoracic surgery or other intervention. Management of this complication includes conservative measures, surgical exploration/ligation, and percutaneous thoracic duct embolization. This case presents a medically complex patient with persistent chylous effusions after thoracoscopic resection of a fluorodeoxyglucose (FDG) and Cu 64 DOTATATE-avid retrocrural lymph node. Initial conventional fluoroscopic lymphangiogram and thoracic duct embolization were unsuccessful. Subsequent magnetic resonance lymphangiography (MRL) more accurately localized the leak which was then marked with computed tomography-guided needle placement before conversion to fluoroscopically guided embolization. This case demonstrates the utility of MRL as a problem-solving tool for localizing hard-to-treat lymphatic leaks. MRL localized embolization is a safe and effective treatment for lymphatic leaks.

Effective neuromotor function may be considered the combination of activating motor units of a type, matching the desired force and fatigue requirements of a behaviour; and the timing of these activations in concert with motor units of other motor pools and/or with contextual/sensory cues. Although the former is well-established as being impaired with age (i.e., sarcopenia), the latter timing issues remain poorly defined in terms of aging. Indeed, sarcopenia may be considered the apotheosis of a degenerative process that first affects the timing and effective activation of motor units prior to overt weakness. We hypothesized that mild motor impairment (i.e., timing deficiencies and motor neuron synaptic pathology) would precede overt striated muscle weakness and motor neuron death. To test this hypothesis, we evaluated the neuromotor system for swallow, where striated muscle activities do not create torque across a joint (a confounder in aging studies) but pressure in the oropharynx and coordination with ventilation. We used female and male Fischer 344 rats (F344) at 6- (young), 18- (late middle-age) and 24-months-old (old) rats. Behavioral evaluations consisted of pharyngeal and thoracic pressures during naturalistic (0.5 ml oral water bolus) swallow. Synapse evaluations consisted of golgi-cox evaluation of nucleus ambiguus and hypoglossal motor neurons, and serial blockface electron microscopy evaluation of hypoglossal motor neurons. We assessed longitudinal (intrinsic) and genioglossus (extrinsic) muscle function and histopathology using platinum plate electrodes and immunohistochemistry for myosin heavy chain (MyHC) expression, respectively. Overall, we show that swallow timing abnormalities occur at late middle-age, contemporaneous with dendritic synaptic and mitochondrial deficits. Notably, motor neuron survival and muscle function and cross-sectional areas were unchanged in late middle- age, with sarcopenia and nucleus ambiguus and hypoglossal motor neuron death only apparent from old age. These results are consistent with the concept of “mild motor impairment” being a harbinger of striated muscle sarcopenia and frailty. There is every reason to suggest that these early motor timing deficits occur in spinal motor neurons. These results illustrate the importance motor neuron health has on maintenance of motor function into old age. Funding: This study was supported by R56 HL166204 & R01 AG086136 (MJF) 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.

Sarcopenia is the age-associated muscle weakness and atrophy. As this muscle weakens, so does the capacity for an animal to perform its associated behaviors. The tibialis anterior (TA) muscle is a lower leg muscle that is important for dorsiflexion during actions such as jumping and running. In humans and Fischer 344 rats, behavioral and pathophysiological assessments show spinal cord motor unit dysfunctions with age are primarily of fast fatigueable motor units, comprising larger MN and the type IIx/b fibers they innervate. In addition, mitochondrial dysfunctions are implicated in aging neuromotor dysfunction and muscle weakness, however, little fiber type specific knowledge exists regarding the function of aged mitochondria in type-identified muscle fibers. Based on the specific atrophy and reduced oxidative capacity (succinate dehydrogenase [SDH] enzymatic function) of type IIx/b fibers in respiratory muscle, we expected to observe type-specific atrophy and reduced SDH activity in type IIx/b TA fibers. In young (6-months-old, n=12) and old (24-months-old, n=12) female and male F344 rats, cut serial TA sections (8 µm) on a cryostat to evaluate type specific morphology and SDH. To determine CSA TA fibers were labelled with MyHCSlow (Novus NBP2 50299), MyHC2A (Novus N1551) and anti-Laminin antibodies, with alexa488, alexa555 and alexa408 secondaries, respectively. SDH was determined using 10 min incubation n 80 mM succinate with 1.5mM nitro blue tetrazolium, with precipitate imaged using a Nikon AR1 inverted microscope with a 579nm high pass filter. We observed a fiber type-specific atrophy of IIx/b fibers in old TA fibers. We also observed a marked reduction in TA SDH activity in old age, confined to type IIx/b fibers. These findings illustrate consistent fast fatigue resistant motor unit degeneration in old age. Strategies specifically targeted to these motor units are imperative in interventions of sarcopenia. Funding: This study was supported by R56 HL166204 (MJF), R01 AG086136 (MJF) and AG44615 (GCS) from the NIH. 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.

Brain derived neurotrophic factor (BDNF) signals through its high-affinity full-length tropomyosin receptor kinase-B (TrkB.FL) and plays role in maintaining the survival and function of phrenic motor neurons (PhMNs), neuromuscular transmission and synaptic activity. Disruption of this pathway is a hallmark of several neurodegenerative diseases associated with dysfunction and death of PhMNs with impaired mitochondrial function. BDNF/TrkB.FL signaling phosphorylates CREB at serine 133 (pCREBS133) and promotes its nuclear localization in cervical ventral horn of rats, however its downstream molecular pathway has not yet been established. Recently, we demonstrated that in human airway smooth muscle cells, pCREBS133, as a transcription factor, binds to the CRE sequence in the PGC1a promoter and activates its expression. PGC1a co-transcriptionally activates mitochondrial transcription factor A (TFAM) expression promoting mitochondrial DNA (mtDNA) replication and mitochondrial biogenesis. In the present study, we hypothesized that BDNF/TrkB.FL signaling promotes pCREBS133 phosphorylation and transcriptional activation of PGC1a and downstream expression of TFAM, leading to mitochondrial biogenesis. In this study, we employed a loss of function approach using a novel chemogenetic rat model (TrkBF616A) with a knock-in allele sensitive to the selective kinase inhibitor 1NMPP1 to inhibit TrkB.FL kinase activity. One group of female and male rats were treated intrathecally at C4 with either artificial cerebrospinal fluid (aCSF) or BDNF (450 ng/ 300 g b.w.; diluted in aCSF) for 40 mins, followed by collection of C3-C6 cervical ventral horn. In a second group, female and male rats were treated with 1NMPP1 (25 uM; i.p.) or the vehicle DMSO for 2 h. After 2 h, both groups were treated intrathecally with BDNF for 40 min and the C3-C6 cervical ventral horn collected. Intrathecal BDNF increased the pTrkB.FLY817 autophosphorylation and downstream phosphorylation of pCREBS133. Bioinformatic analysis identified a putative binding site of pCREBS133 on PGC1a promoter, which was confirmed by Chromatin immunoprecipitation (ChIP) assay. Consistent with this, BDNF treatment increased the expression of PGC1a and downstream TFAM, with an increase in mtDNA copy number. 1NMPP1 inhibition of TrkB.FL kinase (blunted BDNF-induced pTrkB.FLY817 phosphorylation) inhibited downstream activation of the pCREBS133/PGC1a/TFAM signaling cascade. Additionally, 1NMPP1 treatment blunted the BDNF-induced increase in mtDNA copy number. We conclude that BDNF/TrKB.FL signaling mediates mitochondrial biogenesis in the cervical ventral horn suggesting that interventions targeting this pathway could be a therapeutic strategy for neurodegenerative diseases. This research was funded by NIH Grants HL146114 & AG44615. 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.

In the aerodigestive system (ventilation, swallow, speech and airway defense manoeuvres), age-related neuromotor declines contribute to the increased risk of aspiration pneumonia, a leading cause of mortality in the elderly. In the Fischer 344 (F344) rat model, we and others have identified that brainstem hypoglossal motor neuron (MN) degenerations and death contribute to motor dyscoordination and tongue muscle weakness, respectively. In F344 rats, both MNs and striated muscle exhibit morphological and functional deficits of mitochondria in aging, consistent with elderly human post mortem results. However, to date the dendritic and axonal compartments have been relatively ignored. In young (6-months old; n=6 rats) and old (24-months-old; n=6 rats) female and male F344 hypoglossal motor axons were assessed using serial block face scanning electron microscopy (SDFEM). Within myelinated hypoglossal motor axons and hypoglossal MN dendrites, mitochondrial volume density and morphology (mitochondrial CSA, form factor and aspect ratios) were assessed. In old age, mitochondrial volume density was reduced in dendrites and, surprisingly, increased in axons. Mitochondrial fragmentation (reduced CSA, form factors and aspect ratios was apparent in dendrites. In axons, old age mitochondria were larger, but more simplistic. We interpret these dendritic findings to be consistent with altered neural network function in old age. In the axons, excessive mitochondria may physically impair the anterograde and retrograde transit along the axons. Our results suggest that a more nuanced compartment-specific evaluation of mitochondrial structure and function is required to fully elucidate the pathophysiology underlying age-related neuromotor dysfunction. Funding for this research was provided by National Institutes of Health (NIH) grant AG086136 (MJF). 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.

Tongue-muscle associated behaviours (swallow, speech) are impaired in the elderly. In the Fischer 344 (F344) rat model of aging, hypoglossal MNs and intrinsic tongue muscle weakness and atrophy are evident. Here we evaluated young (6-months; n=6 rats) and old (24-months-old; n=6 rats) F344 rat longitudinal muscles for neuromuscular junction (NMJ) innervation. In 140 µm free floating sections, presynaptic components were labelled with synaptophysin and neurofilament. Postsynaptic acetylcholine receptors were labelled with α-Bungarotoxin. NMJs were imaged using confocal microscopy with presynaptic invasion of the postsynaptic endplate quantified (n=200 young NMJs, n=180 old NMJs). We found marked denervation of tongue NMJs in old age,. Our findings underpin the significant role that tongue dysfunction has in the increased risk of aspiration pneumonia and obstructive sleep apnea in the elderly. This study was supported by R56 HL166204 (MJF), R01 AG086136 (MJF) and AG44615 (GCS) from the NIH. 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.

The motor unit consists of an individual motor neuron (MN) and the muscle fibers it innervates. In humans and rodents, muscle weakness in aging (sarcopenia) has focused on altered motor unit discharge properties and intrinsic skeletal muscle pathophysiology, with MNs relatively ignored. In the brainstem, the intrinsic and extrinsic tongue muscles are innervated by hypoglossal MNs. In the spinal cord, the hindlimb muscles are innervated by the lumbar motor enlargement. Both aerodigestive and locomotor behaviours are affected in old age. In Fischer 344 rats, age-related MN death is evident by 24 months, disproportionately affecting larger (likely fast fatiguable motor unit) MNs. Here, we evaluated hypoglossal and lumbar MN survival in female and male Sprague Dawley rats at young (6-months-old; n=12) and old (24-months-old; n=6) ages. Stereological assessment of hypoglossal MN numbers and surface areas were performed on 16 µm Nissl-stained brainstem and spinal cord cryosections. We observed a robust loss of ~20% of hypoglossal MNs and a modest ~15% reduction in their surface areas with age. In the larger size tertile of hypoglossal MNs, age-associated loss of MNs approached ~30%. Similarly, we observed an ~20% lumbar MN loss, with a striking ~25% reduction in somal surface area. In the larger size tertile of lumbar MNs, age-associated loss of MNs approached ~40%. These findings underscore a marked neurogenic component to age-related neuromotor dysfunction, with reliability of findings across rat strains. This MN death likely contribute to physiologically relevant aerodigestive and locomotor impairments in old age. This study was supported by R56 HL166204 (MJF), R01 AG086136 (MJF) and AG44615 (GCS) from the NIH. 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.