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Neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. We induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of LPS. Here, we show that, during chorioamnionitis, the amnion upregulated phospho-IRAK1-expressed neutrophil chemoattractants CXCL8 and CSF3 in an IL-1-dependent manner. IL-1R blockade decreased chorio-decidua neutrophil accumulation, neutrophil activation, and IL-6 and prostaglandin E2 concentrations in the amniotic fluid. Neutrophils accumulating in the chorio-decidua had increased survival mediated by BCL2A1, and IL-1R blockade also decreased BCL2A1+ chorio-decidua neutrophils. Readouts for inflammation in a cohort of women with preterm delivery and chorioamnionitis were similar to findings in the rhesus macaques. IL-1 is a potential therapeutic target for chorioamnionitis and associated morbidities.

Background: Cynomolgus monkeys (Macaca fascicularis) are essential in biomedical research, including reproductive studies. However, the application of human estimated foetal weight (EFW) formulas using ultrasonography (USG) in these non‐human primates is not well established. Objectives: This study aims to evaluate the applicability of human EFW formulas for estimating foetal weight in cynomolgus monkeys at approximately 130 days of gestation. Methods: Our study involved nine pregnant cynomolgus monkeys. We measured foetal parameters, including biparietal diameter, head circumference, abdominal circumference and femur length using USG. The EFW was calculated using 11 human EFW formulas. The actual birthweight (ABW) was recorded following Cesarean section, the day after the EFW calculation. For comparing EFW and ABW, we employed statistical methods such as mean absolute percentage error (APE) and Bland–Altman analysis. Results: The ABW ranged between 200.36 and 291.33 g. Among the 11 formulas, the Combs formula showed the lowest APE (4.3%) and highest correlation with ABW (p < 0.001). Notably, EFW and ABW differences for the Combs formula were ≤5% in 66.7% and ≤10% in 100% of cases. The Bland–Altman analysis supported these results, showing that all cases fell within the limits of agreement. Conclusions: The Combs formula is applicable for estimating the weight of cynomolgus monkey fetuses with USG at approximately 130 days of gestation. Our observations suggest that the Combs formula can be applied in the prenatal care and biomedical research of this species. [ABSTRACT FROM AUTHOR]

Objective: We investigated whether hippocampal perfusion changes are associated with cognitive decline, motor deficits, and the risk of dementia conversion in patients with Parkinson disease (PD). Methods: We recruited patients with newly diagnosed and nonmedicated PD and healthy participants who underwent dual phase 18F‐N‐(3‐fluoropropyl)‐2β‐carboxymethoxy‐3β‐(4‐iodophenyl) nortropane positron emission tomography scans. Patients were classified into 3 groups according to hippocampal perfusion measured by standard uptake value ratios (SUVRs): (1) PD hippocampal hypoperfusion group (1 standard deviation [SD] below the mean hippocampal SUVR of healthy controls; PD‐hippo‐hypo), (2) PD hippocampal hyperperfusion group (1 SD above the mean; PD‐hippo‐hyper), and (3) the remaining patients (PD‐hippo‐normal). We compared the baseline cognitive performance, severity of motor deficits, hippocampal volume, striatal dopamine transporter (DAT) availability, and risk of dementia conversion among the groups. Results: We included 235 patients (PD‐hippo‐hypo, n = 21; PD‐hippo‐normal, n = 157; PD‐hippo‐hyper, n = 57) and 48 healthy participants. Patients in the PD‐hippo‐hypo group were older and had smaller hippocampal volumes than those in the other PD groups. The PD‐hippo‐hypo group showed less severely decreased DAT availability in the putamen than the other groups despite similar severities of motor deficit. The PD‐hippo‐hypo group had a higher risk of dementia conversion compared to the PD‐hippo‐normal (hazard ratio = 2.59, p = 0.013) and PD‐hippo‐hyper (hazard ratio = 3.73, p = 0.006) groups, despite similar cognitive performance at initial assessment between groups. Interpretation: Hippocampal hypoperfusion may indicate a reduced capacity to cope with neurodegenerative processes in terms of the development of motor deficits and cognitive decline in patients with PD. ANN NEUROL 2024;95:388–399 [ABSTRACT FROM AUTHOR]

The common marmoset (Callithrix jacchus) is considered an ideal species for developing genetically modified nonhuman primates (NHP) models of human disease, particularly eye disease. They have been proposed as a suitable bridge between rodents and other NHP models due to their similar ophthalmological features to humans. Prenatal ultrasonography is an accurate and reliable diagnostic tool for monitoring fetal development and congenital malformation. We monitored fetal eye growth and development using noninvasive ultrasonography in 40 heads of clinically normal fetuses during pregnancy to establish the criteria for studying congenital eye anomalies in marmosets. The coronal, sagittal, and transverse planes were useful to identify the facial structures for any associated abnormalities. For orbital measurements, biorbital distance (BOD), ocular diameter (OD), interorbital distance (IOD), and total axial length (TAL) were measured in the transverse plane and carefully identified for intraorbital structures. As a result, high correlations were observed between delivery‐based gestational age (GA) and biparietal diameter (BPD), BOD, OD, and TAL. The correlation assessments based on BOD provide more reliable results for monitoring eye growth and development in normal marmosets than any other parameters since BOD has the highest correlation coefficient according to both delivery‐based GA and BPD among ocular measurements. In conclusion, orbital measurements by prenatal ultrasonography provide reliable indicators of marmoset eye growth, and it could offer early diagnostic criteria to facilitate the development of eye disease models and novel therapies such as genome editing technologies in marmosets. Research highlights: Prenatal ultrasound was used to evaluate fetal growth and eye development in 40 clinically normal marmoset fetuses. It identified a high correlation between delivery‐based gestational age (GA) and parietal diameter (BPD), one of the biometrics for assessing fetal size. In addition, high correlations were observed between the delivery‐based GA and the ocular development biometrics, including biorbital distance (BOD), orbital diameter (OD), and total axial length (TAL).Correlation evaluation based on BOD provided more reliable results for monitoring eye development in normal marmosets since BOD has the highest correlation coefficient according to delivery‐based GA and BPD among ocular measurements.Prenatal ultrasonography is an easy and noninvasive method in marmosets and provides reliable results for evaluating fetal viability and eye growth. [ABSTRACT FROM AUTHOR]