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Background Pulmonary artery stenosis, neoaortic dilatation, and neoaortic valve insufficiency are among the most frequent complications of the arterial switch operation for repair of dextro-transposition of the great arteries (d-TGA). It remains difficult to predict which patients will require great arterial reintervention. Objective We aimed to characterize hemodynamics within the great arteries using 4D flow MRI in patients with d-TGA after the arterial switch operation. Materials and methods Patients with d-TGA after the arterial switch operation and controls with normal cardiac anatomy who underwent 4D flow MRI between 2012 and 2024 were included in this IRB-approved retrospective cohort study. Controls included patients undergoing MRI for other indications who consented or assented to the addition of a 4D flow sequence, as well as patients who underwent clinically indicated 4D flow MRI and were found to have normal cardiac anatomy and function. Velocity, stasis, kinetic energy, energy loss, wall shear stress, and pulse wave velocity were quantified in the aorta and pulmonary arteries. To compare each parameter between d-TGA patients and controls, unpaired t -tests were used for normally distributed data and Mann–Whitney tests for non-normal data. P  < 0.05 was significant. Results Patients with d-TGA after the arterial switch operation (15.7 years ± 2.4, 2 females) demonstrated significantly higher maximum and mean velocity, maximum and mean kinetic energy, energy loss, and maximum and mean wall shear stress within the pulmonary arteries ( P  < 0.0001 for all parameters) compared with age-matched controls (15.5 years ± 2.4, 14 females). Aortic maximum ( P  = 0.001) and mean ( P  = 0.048) velocity, maximum ( P  = 0.0008) and mean ( P  = 0.003) kinetic energy, energy loss ( P  < 0.0001), maximum wall shear stress in five of six regions (range P  < 0.0001 to P  = 0.002), and mean wall shear stress in three regions (range P  = 0.005 to P  = 0.03) were significantly higher in patients with d-TGA after the arterial switch operation patients compared with age-matched controls. Conclusion Patients with d-TGA after the arterial switch operation demonstrate hemodynamic abnormalities within the great arteries, which may provide insight into the mechanisms underlying postoperative consequences of the arterial switch operation. Graphical Abstract

Purpose Intraventricular hemorrhage (IVH) of prematurity can lead to hydrocephalus, sometimes necessitating permanent cerebrospinal fluid (CSF) diversion. We sought to characterize the relationship between head circumference (HC) and ventricular size in IVH over time to evaluate the clinical utility of serial HC measurements as a metric in determining the need for CSF diversion. Methods We included preterm infants with IVH born between January 2000 and May 2020. Three measures of ventricular size were obtained: ventricular index (VI), Evan’s ratio (ER), and frontal occipital head ratio (FOHR). The Pearson correlations ( r ) between the initial (at birth) paired measurements of HC and ventricular size were reported. Multivariable longitudinal regression models were fit to examine the HC:ventricle size ratio, adjusting for the age of the infant, IVH grade (I/II vs. III/IV), need for CSF diversion, and sex. Results A total of 639 patients with an average gestational age of 27.5 weeks were included. IVH grade I/II and grade III/IV patients had a positive correlation between initial HC and VI ( r  = 0.47, p  < 0.001 and r  = 0.48, p  < 0.001, respectively). In our longitudinal models, patients with a low-grade IVH (I/II) had an HC:VI ratio 0.52 higher than those with a high-grade IVH ( p -value < 0.001). Patients with low-grade IVH had an HC:ER ratio 12.94 higher than those with high-grade IVH ( p -value < 0.001). Patients with low-grade IVH had a HC:FOHR ratio 12.91 higher than those with high-grade IVH ( p -value < 0.001). Infants who did not require CSF diversion had an HC:VI ratio 0.47 higher than those who eventually did ( p  < 0.001). Infants without CSF diversion had an HC:ER ratio 16.53 higher than those who received CSF diversion ( p  < 0.001). Infants without CSF diversion had an HC:FOHR ratio 15.45 higher than those who received CSF diversion (95% CI (11.34, 19.56), p  < 0.001). Conclusions There is a significant difference in the ratio of HC:VI, HC:ER, and HC:FOHR size between patients with high-grade IVH and low-grade IVH. Likewise, there is a significant difference in HC:VI, HC:ER, and HC:FOHR between those who did and did not have CSF diversion. The routine assessments of both head circumference and ventricle size by ultrasound are important clinical tools in infants with IVH of prematurity.

The aim of this study was to test whether post-stroke oral administration of a small molecule p75 neurotrophin receptor (p75NTR) modulator (LM11A-31) can augment neuronal survival and improve recovery in a mouse model of stroke. Mice were administered LM11A-31 for up to 12 weeks, beginning 1 week after stroke. Metabolomic analysis revealed that after 2 weeks of daily treatment, mice that received LM11A-31 were distinct from vehicle treated mice by principal component analysis and had higher levels of serotonin, acetylcholine, and dopamine in their ipsilateral hemisphere. LM11A-31 treatment also improved redox homeostasis by restoring reduced glutathione. It also offset a stroke induced reduction in glycolysis by increasing acetyl-CoA. There was no effect on cytokine levels in the infarct. At 13 weeks following stroke, adaptive immune cell infiltration in the infarct was unchanged in LM11A-31 treated mice, indicating that LM11A-31 does not alter the chronic inflammatory response to stroke at the site of the infarct. However, LM11A-31 treated mice had less brain atrophy, neurodegeneration, tau pathology, and microglial activation in other regions of the ipsilateral hemisphere. These findings correlated with improved recovery of motor function on a ladder test, improved sensorimotor and cognitive abilities on a nest construction test, and less impulsivity in an open field test. These data support small molecule modulation of the p75 neurotrophin receptor for preserving neuronal health and function during stroke recovery. The findings from this study introduce the p75 neurotrophin receptor as a novel small molecule target for promotion of stroke recovery. Given that LM11A-31 is in clinical trials as a potential therapy for Alzheimer’s disease, it could be considered as a candidate for assessment in stroke or vascular dementia studies.

Globally, more than 67 million people are living with the effects of ischemic stroke. Importantly, many stroke survivors develop a chronic inflammatory response that contributes to cognitive impairment, a common and debilitating sequela of stroke that is insufficiently studied and currently untreatable. 2-hydroxypropyl-β-cyclodextrin (HPβCD) is an FDA-approved cyclic oligosaccharide developed to solubilize and entrap lipophilic substances. The goal of the present study was to determine whether the repeated administration of HPβCD curtails the chronic inflammatory response to stroke by reducing lipid accumulation within stroke infarcts in a distal middle cerebral artery occlusion + hypoxia (DH) mouse model of stroke. We subcutaneously injected young adult and aged mice with vehicle or HPβCD three times per week for up to 7 weeks following stroke and evaluated them using immunostaining, RNA sequencing, lipidomics, and behavioral analyses. Chronic stroke infarct and peri-infarct regions of HPβCD-treated mice were characterized by an upregulation of genes involved in lipid metabolism and a downregulation of genes involved in innate and adaptive immunity, reactive astrogliosis, and chemotaxis. Correspondingly, HPβCD reduced the accumulation of lipid droplets, T lymphocytes, B lymphocytes, and plasma cells in stroke infarcts. Repeated administration of HPβCD also improved recovery through the preservation of neurons in the striatum and thalamus, induction of c-Fos in hippocampal regions, protection of hippocampal-dependent spatial working memory, and reduction in impulsivity at 7 weeks after stroke. These results indicate that systemic HPβCD treatment following stroke attenuates chronic inflammation and secondary neurodegeneration and prevents post-stroke cognitive decline. Competing Interest Statement The authors have declared no competing interest. Footnotes * https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173544 * https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE173715

The asynchrony of cytoplasmic and nuclear maturation in cumulus–oocyte complexes (COCs) due to prematurely declining concentrations of cyclic adenosine monophosphate (cAMP) has been shown to result in reduced oocyte developmental competence. The objective of this study was to evaluate the effect of pre-IVM treatment with cAMP modulators for different durations on the developmental potential of equine oocytes used for cloned embryo production. Collected COCs were transferred to cryovials filled with transport medium at 20–22 °C. Within the cryovials, the COCs were either untreated (Control) for 18 h or treated with 50 µM forskolin and 100 µM 3-isobutyl-1-methylxanthine for the first 4 h (Pre-IVM 4 h) or the entire 18 h (Pre-IVM 18 h). Oocytes were then transferred to maturation medium and incubated for a further 22–24 h at 38.5 °C in 5% CO2 in air. Somatic cell nuclear transfer embryos were then produced using the meiotically mature oocytes and donor cells from six different fibroblast cell lines. The rates of maturation and embryo development did not differ significantly between the groups, though blastocyst formation tended to be inferior in the Pre-IVM 4 h group compared with the Control group (p = 0.06). Of 67 blastocysts produced, 23 were transferred to recipient mares on Day 4 or 5 post-ovulation. Regarding the pregnancy outcomes, no significant differences were found between the groups, and four viable foals were born, each derived from a different donor cell line. The findings expand on those from previous evaluations of this biphasic IVM system, and indicate that the cAMP-modulating treatments exert limited effects under the pre-IVM conditions used here.