Prenatal tetrahydrocannabinol and cannabidiol exposure produce sex-specific pathophysiological phenotypes in the adolescent prefrontal cortex and hippocampus.

Clinical and preclinical evidence has demonstrated an increased risk for neuropsychiatric disorders following prenatal cannabinoid exposure. However, given the phytochemical complexity of cannabis, there is a need to understand how specific components of cannabis may contribute to these neurodevelopmental risks later in life. To investigate this, a rat model of prenatal cannabinoid exposure was utilized to examine the impacts of specific cannabis constituents (Δ9-tetrahydrocannabinol [THC]; cannabidiol [CBD]) alone and in combination on future neuropsychiatric liability in male and female offspring. Prenatal THC and CBD exposure were associated with low birth weight. At adolescence, offspring displayed sex-specific behavioural changes in anxiety, temporal order and social cognition, and sensorimotor gating. These phenotypes were associated with sex and treatment-specific neuronal and gene transcriptional alterations in the prefrontal cortex, and ventral hippocampus, regions where the endocannabinoid system is implicated in affective and cognitive development. Electrophysiology and RT-qPCR analysis in these regions implicated dysregulation of the endocannabinoid system and balance of excitatory and inhibitory signalling in the developmental consequences of prenatal cannabinoids. These findings reveal critical insights into how specific cannabinoids can differentially impact the developing fetal brains of males and females to enhance subsequent neuropsychiatric risk.

Diagnosis of placenta accreta spectrum using ultrasound texture feature fusion and machine learning.

INTRODUCTION: Placenta accreta spectrum (PAS) is an obstetric disorder arising from the abnormal adherence of the placenta to the uterine wall, often leading to life-threatening complications including postpartum hemorrhage. Despite its significance, PAS remains frequently underdiagnosed before delivery. This study delves into the realm of machine learning to enhance the precision of PAS classification. We introduce two distinct models for PAS classification employing ultrasound texture features. METHODS: The first model leverages machine learning techniques, harnessing texture features extracted from ultrasound scans. The second model adopts a linear classifier, utilizing integrated features derived from 'weighted z-scores'. A novel aspect of our approach is the amalgamation of classical machine learning and statistical-based methods for feature selection. This, coupled with a more transparent classification model based on quantitative image features, results in superior performance compared to conventional machine learning approaches. RESULTS: Our linear classifier and machine learning models attain test accuracies of 87 % and 92 %, and 5-fold cross validation accuracies of 88.7 (4.4) and 83.0 (5.0), respectively. CONCLUSIONS: The proposed models illustrate the effectiveness of practical and robust tools for enhanced PAS detection, offering non-invasive and computationally-efficient diagnostic tools. As adjunct methods for prenatal diagnosis, these tools can assist clinicians by reducing the need for unnecessary interventions and enabling earlier planning of management strategies for delivery.

Head movement dynamics in dystonia: a multi-centre retrospective study using visual perceptive deep learning.

Dystonia is a neurological movement disorder characterised by abnormal involuntary movements and postures, particularly affecting the head and neck. However, current clinical assessment methods for dystonia rely on simplified rating scales which lack the ability to capture the intricate spatiotemporal features of dystonic phenomena, hindering clinical management and limiting understanding of the underlying neurobiology. To address this, we developed a visual perceptive deep learning framework that utilizes standard clinical videos to comprehensively evaluate and quantify disease states and the impact of therapeutic interventions, specifically deep brain stimulation. This framework overcomes the limitations of traditional rating scales and offers an efficient and accurate method that is rater-independent for evaluating and monitoring dystonia patients. To evaluate the framework, we leveraged semi-standardized clinical video data collected in three retrospective, longitudinal cohort studies across seven academic centres. We extracted static head angle excursions for clinical validation and derived kinematic variables reflecting naturalistic head dynamics to predict dystonia severity, subtype, and neuromodulation effects. The framework was also applied to a fully independent cohort of generalised dystonia patients for comparison between dystonia sub-types. Computer vision-derived measurements of head angle excursions showed a strong correlation with clinically assigned scores. Across comparisons, we identified consistent kinematic features from full video assessments encoding information critical to disease severity, subtype, and effects of neural circuit interventions, independent of static head angle deviations used in scoring. Our visual perceptive machine learning framework reveals kinematic pathosignatures of dystonia, potentially augmenting clinical management, facilitating scientific translation, and informing personalized precision neurology approaches.

Impact of maternal posture on fetal physiology in human pregnancy: a narrative review.

In numerous medical conditions, including pregnancy, gravity and posture interact to impact physiology and pathophysiology. Recent investigations, for example, pertaining to maternal sleeping posture during the third trimester and possible impact on fetal growth and stillbirth risk highlight the importance and potential clinical implications of the subject. In this review, we provide an extensive discussion of the impact of maternal posture on fetal physiology from conception to the postpartum period in human pregnancy. We conducted a systematic literature search of the MEDLINE database and identified 242 studies from 1991 through 2021, inclusive, that met our inclusion criteria. Herein, we provide a synthesis of the resulting literature. In the first section of the review, we group the results by the impact of maternal posture at rest on the cervix, uterus, placenta, umbilical cord, amniotic fluid, and fetus. In the second section of the review, we address the impact on fetal-related outcomes of maternal posture during various maternal activities (e.g., sleep, work, exercise), medical procedures (e.g., fertility, imaging, surgery), and labor and birth. We present the published literature, highlight gaps and discrepancies, and suggest future research opportunities and clinical practice changes. In sum, we anticipate that this review will shed light on the impact of maternal posture on fetal physiology in a manner that lends utility to researchers and clinicians who are working to improve maternal, fetal, and child health.

Symmetry-Shaped Singularities in High-Temperature Superconductor H3S.

The superconducting critical temperature of H3S ranks among the highest measured, at 203 K. This impressive value stems from a singularity in the electronic density-of-states, induced by a flat-band region that consists of saddle points. The peak sits right at the Fermi level, so that it gives rise to a giant electron-phonon coupling constant. In this work, we show how atomic orbital interactions and space group symmetry work in concert to shape the singularity. The body-centered cubic Brillouin Zone offers a unique 2D hypersurface in reciprocal space: fully connecting squares with two different high-symmetry points at the corners, Γ and H, and a third one in the center, N. Orbital mixing leads to the collapse of fully connected 1D saddle point lines around the square centers, due to a symmetry-enforced s-p energy inversion between Γ and H. The saddle-point states are invariably nonbonding, which explains the unconventionally weak response of the superconductor's critical temperature to pressure. Although H3S appears to be a unique case, the theory shows how it is possible to engineer flat bands and singularities in 3D lattices through symmetry considerations.

Virological Traits of the SARS-CoV-2 BA.2.87.1 Lineage.

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for efficient spread in the population.

Epidemiological and clinical description of patients with oropharyngeal cancer treated in a public oncology referral hospital in Chile.

Introduction: The incidence of squamous carcinoma of the oropharynx (OPSCC) has presented an increase worldwide, a fact that occurs along with a phenomenon of epidemiological transition, whose pathogenesis is linked to human papilloma virus (HPV) in a significant part of the cases. Published evidence at the Latin American level is scarce. The present study aims to evaluate the epidemiological and clinical characteristics of patients with oropharyngeal cancer treated in a public oncology reference centre in Chile. Methodology: A cross-sectional study was carried out. Patients with histological confirmation of OPSCC aged 18 years or older, referred to the National Cancer Institute of Chile between 2012 and 2023 were included. The association with HPV was determined by immunohistochemistry for p16. Results: 178 patients were analysed, most of them in locoregionally advanced stages involving the palatine tonsil. Seventy-seven percent were male, with a median age of 60 years. Sixty-seven percent of patients were positive for p16, with a progressive increase to 85% in the last 2 years of the study. The p16(+) patients were younger and had fewer classical risk factors. Primary treatment was radiotherapy in 94% of patients. Conclusion: The epidemiological profile of patients with OPSCC treated in a Chilean public oncology referral centre reflects the epidemiological transition observed in developed countries. This change justifies the need to adapt health policies and conduct research that considers the characteristics of this new epidemiological profile.

Prevalence of trace gas-oxidizing soil bacteria increases with radial distance from Polloquere hot spring within a high-elevation Andean cold desert.

High-elevation arid regions harbor microbial communities reliant on metabolic niches and flexibility to survive under biologically stressful conditions, including nutrient limitation that necessitates the utilization of atmospheric trace gases as electron donors. Geothermal springs present "oases" of microbial activity, diversity, and abundance by delivering water and substrates, including reduced gases. However, it is unknown whether these springs exhibit a gradient of effects, increasing their impact on trace gas-oxidizers in the surrounding soils. We assessed whether proximity to Polloquere, a high-altitude geothermal spring in an Andean salt flat, alters the diversity and metabolic structure of nearby soil bacterial populations compared to the surrounding cold desert. Recovered DNA and metagenomic analyses indicate that the spring represents an oasis for microbes in this challenging environment, supporting greater biomass with more diverse metabolic functions in proximal soils that declines sharply with radial distance from the spring. Despite the sharp decrease in biomass, potential rates of atmospheric hydrogen (H2) and carbon monoxide (CO) uptake increase away from the spring. Kinetic estimates suggest this activity is due to high-affinity trace gas consumption, likely as a survival strategy for energy/carbon acquisition. These results demonstrate that Polloquere regulates a gradient of diverse microbial communities and metabolisms, culminating in increased activity of trace gas-oxidizers as the influence of the spring yields to that of the regional salt flat environment. This suggests the spring holds local importance within the context of the broader salt flat and potentially represents a model ecosystem for other geothermal systems in high-altitude desert environments.

Identification of TFG- and Autophagy-Regulated Proteins and Glycerophospholipids in B Cells.

Autophagy supervises the proteostasis and survival of B lymphocytic cells. Trk-fused gene (TFG) promotes autophagosome-lysosome flux in murine CH12 B cells, as well as their survival. Hence, quantitative proteomics of CH12tfgKO and WT B cells in combination with lysosomal inhibition should identify proteins that are prone to lysosomal degradation and contribute to autophagy and B cell survival. Lysosome inhibition via NH4Cl unexpectedly reduced a number of proteins but increased a large cluster of translational, ribosomal, and mitochondrial proteins, independent of TFG. Hence, we propose a role for lysosomes in ribophagy in B cells. TFG-regulated proteins include CD74, BCL10, or the immunoglobulin JCHAIN. Gene ontology (GO) analysis reveals that proteins regulated by TFG alone, or in concert with lysosomes, localize to mitochondria and membrane-bound organelles. Likewise, TFG regulates the abundance of metabolic enzymes, such as ALDOC and the fatty acid-activating enzyme ACOT9. To test consequently for a function of TFG in lipid metabolism, we performed shotgun lipidomics of glycerophospholipids. Total phosphatidylglycerol is more abundant in CH12tfgKO B cells. Several glycerophospholipid species with similar acyl side chains, such as 36:2 phosphatidylethanolamine and 36:2 phosphatidylinositol, show a dysequilibrium. We suggest a role for TFG in lipid homeostasis, mitochondrial functions, translation, and metabolism in B cells.

Sex-specific Impact of the first COVID-19 Lockdown on Age Structure and Case Acuity at Admission in a Patient Population in southwestern Germany: a retrospective comparative Study in Neuroradiology.

OBJECTIVES: A hard lockdown was presumed to lead to delayed diagnosis and treatment of serious diseases, resulting in higher acuity at admission. This should be elaborated based on the estimated acuity of the cases, changes in findings during hospitalisation, age structure and biological sex. DESIGN: Retrospective monocentric cross-sectional study. SETTING: German Neuroradiology Department at a . PARTICIPANTS: In 2019, n=1158 patients were admitted in contrast to n=884 during the first hard lockdown in 2020 (11th-13th week). MAIN OUTCOME MEASURES: Three radiologists evaluated the initial case acuity, classified them into three groups (not acute, subacute and acute), and evaluated if there was a relevant clinical deterioration. The data analysis was conducted using non-parametric methods and multivariate regression analysis. RESULTS: A 24% decrease in the number of examinations from 2019 to 2020 (p=0.025) was revealed. In women, the case acuity increased by 21% during the lockdown period (p=0.002). A 30% decrease in acute cases in men was observable (in women 5% decrease). Not acute cases decreased in both women and men (47%; 24%), while the subacute cases remained stable in men (0%) and decreased in women (28%). Regression analysis revealed the higher the age, the higher the acuity (p<0.001 in both sexes), particularly among women admitted during the lockdown period (p=0.006). CONCLUSION: The lockdown led to a decrease in neuroradiological consultations, with delays in seeking medical care. In women, the number of most severe cases remained stable, whereas the mean case acuity and age increased. This could be due to greater pandemic-related anxiety among women, however, with severe symptoms they were seeking for medical help. In contrast in men, the absolute number of most severe cases decreased, whereas the mean acuity and age remained nearly unaffected. This could be attributable to a reduced willingness to seek for medical consultation.

Comparing a common clavicle maturation-based age estimation method to ordinary regression analyses with quadratic and sex-specific interaction terms in adolescents.

Established methods of age estimation are based on correlating defined maturation stages of bony structures with tables representing the observed range of biological ages in the majority of cases. In this retrospective monocentric study in southwestern Germany, common age estimation methodology was assessed in n = 198 subjects at the age of 25 or younger by analyzing the influence of age, quadratic age, biological sex and age-sex interaction on the ossification stages of the medial epiphysis fugue. Three readers (ICC ≥ 0.81 for left/right side) evaluated routine care computed tomography images of the clavicle with a slice thickness of 1 mm. By using least square regression analyses, to determine the real biological age a quadratic function was determined corrected for the age estimated by established methods and sex (R2 = 0.6 each side), reducing the mean absolute error and root mean squared error in the age estimation of women (2.57 and 3.19) and men (2.57 and 3.47) to 1.54 and 1.82 for women, and 1.54 and 2.25 for men. In women, the medial clavicle epiphysis seem to fuse faster, which was particularly observable from approximately 18 years of age. Before that age, the estimation method was relatively close to the ideal correlation between assessed and real age. To conclude, the presented new method enables more precise age estimation in individuals and facilitates the determination and quantification of additional variables, quantifying their influence on the maturation of the medial clavicle epiphysis based on the established ossification stages.

GLUT1-mediated glucose import in B cells is critical for anaplerotic balance and humoral immunity.

Glucose uptake increases during B cell activation and antibody-secreting cell (ASC) differentiation, but conflicting findings prevent a clear metabolic profile at different stages of B cell activation. Deletion of the glucose transporter type 1 (GLUT1) gene in mature B cells (GLUT1-cKO) results in normal B cell development, but it reduces germinal center B cells and ASCs. GLUT1-cKO mice show decreased antigen-specific antibody titers after vaccination. In vitro, GLUT1-deficient B cells show impaired activation, whereas established plasmablasts abolish glycolysis, relying on mitochondrial activity and fatty acids. Transcriptomics and metabolomics reveal an altered anaplerotic balance in GLUT1-deficient ASCs. Despite attempts to compensate for glucose deprivation by increasing mitochondrial mass and gene expression associated with glycolysis, the tricarboxylic acid cycle, and hexosamine synthesis, GLUT1-deficient ASCs lack the metabolites for energy production and mitochondrial respiration, limiting protein synthesis. We identify GLUT1 as a critical metabolic player defining the germinal center response and humoral immunity.

Effects of School-Based High-Intensity Interval Training on Hemodynamic Parameters and Heart Rate Variability: A Randomized Controlled Trial.

ABSTRACT: Ketelhut, S, Ketelhut, K, Ketelhut, SR, and Ketelhut, RG. Effects of school-based high-intensity interval training on hemodynamic parameters and heart rate variability: A randomized controlled trial. J Strength Cond Res 38(6): 1033-1040, 2024-The purpose of this study was to assess the effects of a child-specific school-based high-intensity interval training (HIIT) implemented into physical education (PE) classes on various hemodynamic parameters and heart rate variability indices. Forty-six students (age 11 ± 1 year) were randomized into an intervention (INT n = 22) and a control group (CON n = 24). During a 12-week period, the INT and CON groups participated in regular PE twice weekly (45-90 minutes). The INT group received HIIT during the first 20 minutes of the 2 PE classes. Systolic and diastolic blood pressure, total peripheral resistance, aortic pulse wave velocity (aPWV), heart rate, SD of normal to normal heartbeat intervals, the root mean square of successive differences between normal heartbeats (RMSSD), the proportion of differences between adjacent normal to normal heartbeat intervals of more than 50 ms, low-frequency power, high-frequency power, and the LF/HF ratio were assessed before and after the experimental period. A p value ≤0.05 was considered statistically significant. Forty students (20 INT; 20 CON) were included in the analysis. A significant time × group interaction was detected for aPWV ( p = 0.05, η2 = 0.099), RMSSD ( p = 0.010, η2 = 0.161), low-frequency power ( p = 0.009, η2 = 0.165), high-frequency power ( p < 0.001, η2 = 0.272), and the LF/HF ratio ( p < 0.001, η2 = 0.354). The INT group revealed significant improvements for the respective parameters. School-based HIIT can induce improvements in cardiovascular parameters. These results highlight the potential of embedding HIIT within the school setting, offering a time-efficient exercise intervention.

Probing the glioma microvasculature: a case series of the comparison between perfusion MRI and intraoperative high-frame-rate ultrafast Doppler ultrasound.

BACKGROUND: We aimed to describe the microvascular features of three types of adult-type diffuse glioma by comparing dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) with intraoperative high-frame-rate ultrafast Doppler ultrasound. METHODS: Case series of seven patients with primary brain tumours underwent both DSC perfusion MRI and intra-operative high-frame-rate ultrafast Doppler ultrasound. From the ultrasound images, three-dimensional vessel segmentation was obtained of the tumour vascular bed. Relative cerebral blood volume (rCBV) maps were generated with leakage correction and normalised to the contralateral normal-appearing white matter. From tumour histograms, median, mean, and maximum rCBV ratios were extracted. RESULTS: Low-grade gliomas (LGGs) showed lower perfusion than high-grade gliomas (HGGs), as expected. Within the LGG subgroup, oligodendroglioma showed higher perfusion than astrocytoma. In HGG, the median rCBV ratio for glioblastoma was 3.1 while astrocytoma grade 4 showed low perfusion with a median rCBV of 1.2. On the high-frame-rate ultrafast Doppler ultrasound images, all tumours showed a range of rich and organised vascular networks with visually apparent abnormal vessels, even in LGG. CONCLUSIONS: This unique case series revealed in vivo insights about the microvascular architecture in both LGGs and HGGs. Ultrafast Doppler ultrasound revealed rich vascularisation, also in tumours with low perfusion at DSC MRI. These findings warrant further investigations using advanced MRI postprocessing, in particular for characterising adult-type diffuse glioma. RELEVANCE STATEMENT: Our findings challenge the current assumption behind the estimation of relative cerebral blood volume that the distribution of blood vessels in a voxel is random. KEY POINTS: • Ultrafast Doppler ultrasound revealed rich vascularity irrespective of perfusion dynamic susceptibility contrast MRI state. • Rich and organised vascularisation was also observed even in low-grade glioma. • These findings challenge the assumptions for cerebral blood volume estimation with MRI.

SARS-CoV-2 BA.2.86 enters lung cells and evades neutralizing antibodies with high efficiency.

BA.2.86, a recently identified descendant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sublineage, contains ∼35 mutations in the spike (S) protein and spreads in multiple countries. Here, we investigated whether the virus exhibits altered biological traits, focusing on S protein-driven viral entry. Employing pseudotyped particles, we show that BA.2.86, unlike other Omicron sublineages, enters Calu-3 lung cells with high efficiency and in a serine- but not cysteine-protease-dependent manner. Robust lung cell infection was confirmed with authentic BA.2.86, but the virus exhibited low specific infectivity. Further, BA.2.86 was highly resistant against all therapeutic antibodies tested, efficiently evading neutralization by antibodies induced by non-adapted vaccines. In contrast, BA.2.86 and the currently circulating EG.5.1 sublineage were appreciably neutralized by antibodies induced by the XBB.1.5-adapted vaccine. Collectively, BA.2.86 has regained a trait characteristic of early SARS-CoV-2 lineages, robust lung cell entry, and evades neutralizing antibodies. However, BA.2.86 exhibits low specific infectivity, which might limit transmissibility.