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Purpose: Alcohol-related blackouts (ARBs) are common in adolescents and emerging adults. ARBs may also be indicative of persistent, alcohol-related neurocognitive changes. This study explored ARBs as a predictor of altered structural brain development and associated cognitive correlates. Methods: Longitudinal growth curve modeling estimated trajectories of brain volume across 6 years in participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study (n = 800, 213 with lifetime ARB history). While controlling for demographics and overall alcohol use, ARB history was analyzed as a predictor of brain volume growth in regions associated with alcohol-related cognitive change. Post hoc analyses examined whether ARBs moderated relationships between brain morphology and cognition. Results: ARBs significantly predicted attenuated development of fusiform gyrus and hippocampal volume at unique timepoints compared to overall alcohol use. Alcohol use without ARBs significantly predicted attenuated fusiform and hippocampal growth at earlier and later timepoints, respectively. Despite altered development in regions associated with memory, ARBs did not significantly moderate relationships between brain volume and cognitive performance. Conclusion: ARBs and overall alcohol use predicted altered brain development in the fusiform gyrus and hippocampus at different timepoints, suggesting ARBs represent a unique marker of neurocognitive risk in younger drinkers.

The diversity of the plant biomass available on earth makes plants an exceptional resource for replacing fossil resources in green chemistry, bioenergy and biobased materials. For numerous applications, and especially the high-tech ones (building block molecules, high-power bioenergy, additive manufacturing of biobased materials), the macrostructure assemblies of the plant biomass often need to be first broken down into a fine powder. This can be achieved by dry fractionation process combining comminution and sorting steps. The chemical and physical properties of the ground plant powder results both from the process conditions, the histological structure and chemical composition of the raw plant materials. In a forward engineering approach, the quality of the final products can be highly improved by the selection of the right powder (raw materials and production process) for the right application.This article provides production routes together with physical and chemical characterization of 10 biomass powders from 6 different biomass feedstocks (SP - spirulina, HI - hibiscus, PB - pine bark, HC - hemp Core, RH - rice husk and RHA - rice husk ash). These feedstocks represent a broad range of raw materials properties. For pine bark, hemp core, rice husk and rice husk ash, two grades of powders related to two different particle sizes were produced by two different routes to highlight the impact of the comminution process on the powder properties. The devices used and the process parameters are described. The morphological properties of the powder were quantified using laser diffraction (particle size) and image analysis (shape factor) and qualitatively analyzed with SEM. The specific surface area was determined using gas sorption with BET theory, and the hygroscopic properties were measured using direct vapor sorption. The chemical characterizations were determined with a set of biochemical assays and, complementary, FTIR and fluorescence spectra were recorded to provide fingerprints of samples. The dataset includes tables that summarize the main characteristic descriptors of each analysis as well as the raw data.The data are registered in the French Research Data Gouv public repository and also stored in the PO2 BaGaTel database using the PO2/TransformON ontology [1]. SPO2Q web tool allows on line querying of the database, which can also be consulted using PO2 manager desktop application [1–3]

Introduction Several randomised controlled trials have demonstrated that novel oral anticoagulants are safer compared with vitamin K antagonists for the management of non-valvular atrial fibrillation (NVAF) to prevent thromboembolic events in the general population. There is a growing interest in the use of apixaban in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) but there is a lack of randomised data in this population.Methods and analysis APIDP2 is a prospective parallel, randomised, open-label, blinded endpoint trial involving patients with ESRD undergoing chronic PD who have NVAF. A total of 178 participants will be recruited from 20 French PD centres. Eligible patients will be randomly assigned to receive either apixaban at a reduced dose of 2.5 mg two times per day (dose determined with the previous pharmacokinetic study APIDP1) or dose-adjusted to international normalised ratio (INR) target (2–3) coumadin therapy. Anticoagulation to prevent thromboembolic events will be initiated or changed according to the randomisation for a duration of 1 year. The primary outcome is a major or clinically relevant non-major bleeding from randomisation up to month 12, assessed according to the International Society on Thrombosis and Haemostasis Score. Secondary outcomes encompass an efficacy composite criterion combining stroke or transient ischaemic attack (TIA), cardiovascular death and thrombosis including myocardial infarction cumulated at 12 months. Bleeding events will be also classified according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) and Thrombolysis In Myocardial Infarction (TIMI) criteria and pharmacodynamics outcomes will evaluate the time within the INR target range of 2–3 in the warfarin arm over 1 year, and anti-Xa apixaban activity in case of bleeding events and at 1 month, 6 months and 12 months of follow-up in the apixaban arm. To demonstrate that apixaban is safer than warfarin at 1 year, assuming two interim analyses after 60 and 118 patients, a bilateral alpha risk of 5% and a power of 80%, 178 patients are needed in this randomised trial (effect size found from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Study among patients with creatinine clearance 25–30 ml/min), that is, 89 patients per group.Ethics and dissemination The study has been approved by the ethics committee Comité de Protection des Personnes Sud Est III – Lyon - FRANCE, CT number 2023-507544-37-00. Written informed consent is required for each participant. Findings will be presented at scientific meetings and published in peer-reviewed journals.Trial registration ClinicalTrials.gov, NCT06045858; European Clinical Trial System, CT number 2023-507544-37-00.

Abstract Spermatozoa are the cells that are most commonly used for cryopreservation of valuable genetic resources in aquaculture. It is known that fish spermatozoa transmit to the embryo not only their genetic but also their epigenetic profile, especially DNA methylation. Therefore, any alteration of the DNA methylation profile in spermatozoa induces the risk of transmitting epigenetic alterations to the offspring. The aim of this study was to assess the effect of cryopreservation on DNA methylation in rainbow trout spermatozoa. To trigger variable cellular response after freezing–thawing, spermatozoa from mature males were cryopreserved with dimethyl sulfoxide, methanol or glycerol as cryoprotectant. We observed that dimethyl sulfoxide was the best to preserve thawed spermatozoa functions. Methanol only slightly preserved all the cellular parameters, while glycerol failed to protect motility and fertilization ability. The consequences on DNA methylation were assessed using Reduced Representation Bisulfite Sequencing (RRBS). Sperm cryopreservation did not thoroughly impact DNA methylation, although 335–564 differentially methylated cytosines were characterized depending on the cryoprotectant. Very few of them were shared between cryoprotectants, and no correlation with the extent of cellular damage was found. Our study showed that DNA methylation was only slightly altered after sperm cryopreservation, and this may render further analysis of the risk for the progeny very challenging.

This longitudinal study examined the relationship between executive function (EF) and mathematics with rural and urban preschool children. A panel of direct and indirect EF measures were used to compare how well individual measures, as well as analytic approaches, predicted both numeracy and geometry skill. One hundred eighteen children, ages 39 to 68 months, were given EF and mathematics assessments twice, approximately six months apart, concurrent to their teachers completing an indirect assessment of EF for each child. Results suggest: (1) the child's age determines if a panel of direct EF measures is a better predictor of numeracy and geometry skills than a single EF measure, (2) geometry and numeracy skill are influenced differently by contextual factors, and (3) the EF-geometry link may develop about six months later than the EF-numeracy connection. As the relationship between preschool age EF and mathematics is better understood, efforts can be made to improve the aspects of EF connected to mathematics skill, which may aid in performance.

Abstract In poultry, in vitro propagated primordial germ cells (PGCs) represent an important tool for the cryopreservation of avian genetic resources. However, several studies have highlighted sexual differences exhibited by PGCs during in vitro propagation, which may compromise their reproductive capacities. To understand this phenomenon, we compared the proteome of pregonadal migratory male (ZZ) and female (ZW) chicken PGCs propagated in vitro by quantitative proteomic analysis using a GeLC-MS/MS strategy. Many proteins were found to be differentially abundant in chicken male and female PGCs indicating their early sexual identity. Many of the proteins more highly expressed in male PGCs were encoded by genes localised to the Z sex chromosome. This suggests that the known lack of dosage compensation of the transcription of Z-linked genes between sexes persists at the protein level in PGCs, and that this may be a key factor of their autonomous sex differentiation. We also found that globally, protein differences do not closely correlate with transcript differences indicating a selective translational mechanism in PGCs. Male and female PGC expressed protein sets were associated with differential biological processes and contained proteins known to be biologically relevant for male and female germ cell development, respectively. We also discovered that female PGCs have a higher capacity to uptake proteins from the cell culture medium than male PGCs. This study presents the first evidence of an early predetermined sex specific cell fate of chicken PGCs and their sexual molecular specificities which will enable the development of more precise sex-specific in vitro culture conditions for the preservation of avian genetic resources.

Abstract Background The thermal-manipulation (TM) during egg incubation is a cyclic exposure to hot or cold temperatures during embryogenesis that is associated to long-lasting effects on growth performance, physiology, metabolism and temperature tolerance in birds. An increase of the incubation temperature of Japanese quail eggs affected the embryonic and post-hatch survival, growth, surface temperatures and blood characteristics potentially related to thermoregulation capacities. To gain new insights in the molecular basis of TM in quails, we investigated by RNA-seq the hypothalamus transcriptome of 35 days-old male and female quails that were treated by TM or not (C, control) during embryogenesis and that were exposed (HC) or not (RT) to a 36 °C heat challenge for 7 h before sampling. Results For males, 76, 27, 47 and 0 genes were differentially expressed in the CHC vs. CRT, CRT vs. TMRT, TMHC vs. TMRT and CHC vs. TMHC comparisons, respectively. For females, 17, 0, 342 and 1 genes were differentially expressed within the same respective comparisons. Inter-individual variability of gene expression response was observed particularly when comparing RT and HC female animals. The differential expression of several genes was corroborated by RT-qPCR analysis. Gene Ontology functional analysis of the differentially expressed genes showed a prevalent enrichment of terms related to cellular responses to stimuli and gene expression regulation in both sexes. Gene Ontology terms related to the membrane transport, the endoplasmic reticulum and mitochondrial functions as well as DNA metabolism and repair were also identified in specific comparisons and sexes. Conclusions TM had little to no effect on the regulation of gene expression in the hypothalamus of 35 days-old Japanese quails. However, the consequences of TM on gene expression were revealed by the HC, with sex-specific and common functions altered. The effects of the HC on gene expression were most prominent in TM females with a ~ 20-fold increase of the number of differentially expressed genes, suggesting that TM may enhance the gene response during challenging conditions in female quail hypothalamus. TM may also promote new cellular strategies in females to help coping to the adverse conditions as illustrated by the identification of differentially expressed genes related to the mitochondrial and heat-response functions.

Glyphosate (Gly) is the active molecule of non-selective herbicides used in conventional agriculture. Some evidence shows that exposure to Glyphosate-Based Herbicides (GBH) can affect both male and female fertility in animal models. However, few data exist on birds that can be easily exposed through their cereal-based diet. To our knowledge, there are no current studies on the effects of chronic dietary exposure to GBH and the potential reversibility on the fertility and embryo development in chickens. In our protocol, hens (32 weeks-old) were exposed to GBH (47 mg kg-1/day-1 glyphosate equivalent corresponding to half of the No-Observed-Adverse-Effect-Level (NOAEL) as defined by European Food Safety Authority in birds, GBH group (GBH), n = 75) or not (Control group (CT), n = 75) for 6 weeks. Then, both CT and GBH groups were fed for 5 more weeks without GBH exposure. During these two periods, we investigated the consequences on the egg performance and quality, fertilization rate, embryo development, and viability of offspring. Despite the accumulation of Gly and its metabolite aminomethylphosphonic acid (AMPA) in the hen blood plasma, the body weight and laying rate were similar in GBH and CT animals. We observed from the 4th day of exposure an accumulation of Gly (but not AMPA) only in the yolk of the eggs produced by the exposed hens. After artificial insemination of the hens followed by eggs incubation, we showed a strong significant early embryonic mortality level in GBH compared to CT animals (78 ± 2 % vs 2.5 ± 0.3 %, p

Abstract Background Neurocognitive deficits (NCDs) and associated meta-cognition difficulties associated with chronic substance use often delay the learning and change process necessary for addiction recovery and relapse prevention. However, very few cognitive remediation programs have been developed to target NCDs and meta-cognition for substance users. The study described herein aims to investigate the efficacy of a multi-component neurocognitive rehabilitation and awareness program termed “Neurocognitive Empowerment for Addiction Treatment” (NEAT). NEAT is a fully manualized, cartoon-based intervention involving psychoeducation, cognitive practice, and compensatory strategies relevant across 10 major cognitive domains, including aspects of attention, memory, executive functions, and decision-making. Method/design In a single-blind randomized controlled trial (RCT), 80 female opioid and/or methamphetamine users will be recruited from an addiction recovery program providing an alternative to incarceration for women with substance use-related offenses. Eight groups of 9–12 participants will be randomized into NEAT or treatment-as-usual (TAU). NEAT involves 14 90-min sessions, delivered twice weekly. The primary outcome is change in self-reported drug craving from before to after intervention using Obsessive Compulsive Drug Use Scale. Secondary and exploratory outcomes include additional psychological, neurocognitive, and structural and functional neuroimaging measures. Clinical measures will be performed at five time points (pre- and post-intervention, 3-, 6-, and 12-month follow-up); neuroimaging measures will be completed at pre- and post-intervention. Discussion The present RCT is the first study to examine the efficacy of an adjunctive neurocognitive rehabilitation and awareness program for addiction. Results from this study will provide initial information concerning potential clinical efficacy of the treatment, as well as delineate neural mechanisms potentially targeted by this novel intervention. Trial registration ClinicalTrials.gov NCT03922646 . Registered on 22 April 2019

Research Findings: The current study looks at the validity of a voluntary self-report Quality Rating and Improvement System (QRIS) and the characteristics of participating childcare centers. The self-reported quality indicators are compared to external ratings of quality Early Childhood Environment Rating Scale-Revised ([ECERS-R]) and correlated with variables such as size of center and number of state subsidy clients. ECERS-R scores were unrelated to capacity but significantly lower for centers with a large percentage of state-supported clients. Regarding self-reported quality, centers frequently under-reported their quality and what was claimed was not always externally validated, suggesting a self-report QRIS may not be an accurate assessment of quality. Additionally, no significant differences in quality were found between centers participating and those not participating in the self-report QRIS. Practice or Policy: Self-reported childcare quality was not accurate in this study. Although providers over-reported some quality, they frequently under-reported quality, by claiming fewer indicators than external validators found. When centers are unmotivated to participate in a voluntary, self-report QRIS, when items reported are the easiest to report, and when existing quality indicators are unreported, a self-reported QRIS cannot validly reflect quality. Because providers over-reported and under-reported quality criteria, it is doubtful the system truly incentivizes desired quality changes.

Objective: Short‐term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT‐DBS) were reported for people with drug‐resistant focal epilepsy (PwE). Because long‐term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT‐DBS. Methods: In this multicenter registry, PwE with ANT‐DBS were followed up for safety, efficacy, and battery longevity. Follow‐up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%. Results: Of 170 eligible PwE, 104, 62, and 49 completed the 3‐, 4‐, and 5‐year follow‐up, respectively. Most discontinuations (68%) were due to planned study closure as follow‐up beyond 2 years was optional. The 5‐year follow‐up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5‐year follow‐up (p <.001), with most‐pronounced effects on focal‐to‐bilateral tonic–clonic seizures (n = 15, 77% reduction, p =.008). At last follow‐up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy (p =.035) and a negative history of epilepsy surgery (p =.002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS‐related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT‐DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months. Significance: MORE provides further evidence for the long‐term application of ANT‐DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management. [ABSTRACT FROM AUTHOR]

Abstract Background At sexual maturity, the liver of laying hens undergoes many metabolic changes to support vitellogenesis. In published transcriptomic approaches, hundreds of genes were reported to be overexpressed in laying hens and functional gene annotation using gene ontology tools have essentially revealed an enrichment in lipid and protein metabolisms. We reanalyzed some data from a previously published article comparing 38-week old versus 10-week old hens to give a more integrative view of the functions stimulated in the liver at sexual maturity and to move beyond current physiological knowledge. Functions were defined based on information available in Uniprot database and published literature. Results Of the 516 genes previously shown to be overexpressed in the liver of laying hens, 475 were intracellular (1.23–50.72 fold changes), while only 36 were predicted to be secreted (1.35–66.93 fold changes) and 5 had no related information on their cellular location. Besides lipogenesis and protein metabolism, we demonstrated that the liver of laying hens overexpresses several clock genes (which supports the circadian control of liver metabolic functions) and was likely to be involved in a liver/brain/liver circuit (neurotransmitter transport), in thyroid and steroid hormones metabolisms. Many genes were associated with anatomical structure development, organ homeostasis but also regulation of blood pressure. As expected, several secreted proteins are incorporated in yolky follicles but we also evidenced that some proteins are likely participating in fertilization (ZP1, MFGE8, LINC00954, OVOCH1) and in thyroid hormone maturation (CPQ). We also proposed that secreted proteins (PHOSPHO1, FGF23, BMP7 but also vitamin-binding proteins) may contribute to the development of peripheral organs including the formation of medullar bones to provide labile calcium for eggshell formation. Thirteen genes are uniquely found in chicken/bird but not in human species, which strengthens that some of these genes may be specifically related to avian reproduction. Conclusions This study gives additional hypotheses on some molecular actors and mechanisms that are involved in basic physiological function of the liver at sexual maturity of hen. It also revealed some additional functions that accompany reproductive capacities of laying hens, and that are usually underestimated when using classical gene ontology approaches.

Abstract The main objective of ViSEAGO package is to carry out a data mining of biological functions and establish links between genes involved in the study. We developed ViSEAGO in R to facilitate functional Gene Ontology (GO) analysis of complex experimental design with multiple comparisons of interest. It allows to study large-scale datasets together and visualize GO profiles to capture biological knowledge. The acronym stands for three major concepts of the analysis: Visualization, Semantic similarity and Enrichment Analysis of Gene Ontology. It provides access to the last current GO annotations, which are retrieved from one of NCBI EntrezGene, Ensembl or Uniprot databases for several species. Using available R packages and novel developments, ViSEAGO extends classical functional GO analysis to focus on functional coherence by aggregating closely related biological themes while studying multiple datasets at once. It provides both a synthetic and detailed view using interactive functionalities respecting the GO graph structure and ensuring functional coherence supplied by semantic similarity. ViSEAGO has been successfully applied on several datasets from different species with a variety of biological questions. Results can be easily shared between bioinformaticians and biologists, enhancing reporting capabilities while maintaining reproducibility. ViSEAGO is publicly available on https://bioconductor.org/packages/ViSEAGO .

In broiler hens, the genetic selection increased susceptibility to metabolic disorders and reproductive dysfunctions. In human ovarian cells, grape seed extracts (GSE) improved steroid production. Here, we investigated the effects of a GSE dietary supplementation on egg production and quality, fertility parameters, Reactive Oxygen Species (ROS) and steroid content in yolk egg associated to plasma adipokines in broiler hens. For this, we designed two in vivo experiments, the first one included three groups of hens: A (control), B and C (supplemented with GSE at 0.5% and 1% of the total diet composition, respectively, since week 4), and the second one used two groups of hens: A (control) and D (supplemented with GSE at 1% of the total diet composition since hatching). We assessed the egg production from 23th to 40th weeks and quality at 33th week. After artificial inseminations, the fertility parameters were calculated. In egg yolk, Reactive Oxygen Species (ROS) level and steroid production were evaluated by Ros-Glo H202 and ELISA assay, respectively. Expression of steroidogenic enzymes and adipokines and their receptors was determined by RT-qPCR in ovarian cells and plasma adipokines (RARRES2, ADIPOQ and NAMPT) were evaluated by specific ELISA assays. The fertility parameters and egg production were unaffected by GSE supplementation whatever the experiment (exp.). However, the rate of double-yolk eggs decreased for all GSE supplemented groups (exp. 1 P