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Brain functional and structural changes lead to cognitive decline during aging, but a high level of cognitive stimulation during life can improve cognitive performances in the older adults, forming the cognitive reserve. Noradrenaline has been proposed as a molecular link between environmental stimulation and constitution of the cognitive reserve. Taking advantage of the ability of olfactory stimulation to activate noradrenergic neurons of the locus coeruleus, we used repeated olfactory enrichment sessions over the mouse lifespan to enable the cognitive reserve buildup. Mice submitted to olfactory enrichment, whether started in early or late adulthood, displayed improved olfactory discrimination at late ages and interestingly, improved spatial memory and cognitive flexibility. Moreover, olfactory and non-olfactory cognitive performances correlated with increased noradrenergic innervation in the olfactory bulb and dorsal hippocampus. Finally, c-Fos mapping and connectivity analysis revealed task-specific remodeling of functional neural networks in enriched older mice. Long-term olfactory enrichment thus triggers structural noradrenergic plasticity and network remodeling associated with better cognitive aging and thereby forms a promising mouse model of the cognitive reserve buildup., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behavior. To date, no pharmacological treatment has been approved that ameliorates social behavior in patients with ASD. Based on the excitation/inhibition imbalance theory of autism, we hypothesized that bromide ions, long used as an antiepileptic medication, could relieve core symptoms of ASD. We evaluated the effects of chronic sodium bromide (NaBr) administration on autistic-like symptoms in three genetic mouse models of autism: Oprm1 -/- , Fmr1 -/- and Shank3 Δex13-16 -/- mice. We showed that chronic NaBr treatment relieved autistic-like behaviors in these three models. In Oprm1 -/- mice, these beneficial effects were superior to those of chronic bumetanide administration. At transcriptional level, chronic NaBr in Oprm1 null mice was associated with increased expression of genes coding for chloride ions transporters, GABA A receptor subunits, oxytocin and mGlu4 receptor. Lastly, we uncovered synergistic alleviating effects of chronic NaBr and a positive allosteric modulator (PAM) of mGlu4 receptor on autistic-like behavior in Oprm1 -/- mice. We evidenced in heterologous cells that bromide ions behave as PAMs of mGlu4, providing a molecular mechanism for such synergy. Our data reveal the therapeutic potential of bromide ions, alone or in combination with a PAM of mGlu4 receptor, for the treatment of ASDs., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Normal brain aging is associated with deficits in cognitive and sensory processes, due to subtle impairment of synaptic contacts and plasticity. Impairment may be discrete in basal conditions but is revealed when cerebral plasticity is involved, such as in learning contexts. We used olfactory perceptual learning, a non-associative form of learning in which discrimination between perceptually similar odorants is improved following exposure to these odorants, to better understand the cellular bases of olfactory aging in mice. We first evaluated learning ability and memory retention in 2-, 6-, 12-, and 18-month-old mice, and identified 12 months as a pivotal age when memory retention subtly declines before learning becomes totally impaired at later ages. We then showed that learning-induced structural plasticity of adult-born granule cells is specific to cells responding to the learned odorants in the olfactory bulb of young adult mice and loses its specificity in 12-month-old mice, in parallel to memory impairment. Taken together, our data refine our understanding of aging-related impairment of plasticity mechanisms in the olfactory bulb and consequent induction of olfactory learning and memory deficits., (Copyright © 2022. Published by Elsevier Inc.)

COVID-19 has had worse health, education, and labor market effects on groups with low socioeconomic status (SES) than on those with high SES. Little is known, however, about whether COVID-19 has also had differential effects on noncognitive skills that are important for life outcomes. Using panel data from before and during the pandemic, we show that COVID-19 affects one key noncognitive skill, that is, prosociality. While prosociality is already lower for low-SES students prior to the pandemic, we show that COVID-19 infections within families amplify the prosociality gap between French high school students of high and low SES by almost tripling its size in comparison to pre-COVID-19 levels., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Olfactory perceptual learning is defined as an improvement in the discrimination of perceptually close odorants after passive exposure to these odorants. In mice, simple olfactory perceptual learning involving the discrimination of two odorants depends on an increased number of adult-born neurons in the olfactory bulb, which refines the bulbar output. However, the olfactory environment is complex, raising the question of the adjustment of the bulbar network to multiple discrimination challenges. Perceptual learning of 1 to 6 pairs of similar odorants led to discrimination of all learned odor pairs. Increasing complexity did not increase adult-born neuron survival but enhanced the number of adult-born neurons responding to learned odorants and their spine density. Moreover, only complex learning induced morphological changes in neurons of the granule cell layer born during the first day of life (P0). Selective optogenetic inactivation of either population confirmed functional involvement of adult-born neurons regardless of the enrichment complexity, while preexisting neurons were required for complex discrimination only., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: In August 2015, the US Food and Drug Administration (FDA) has approved Addyi ® (flibanserin) for treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in pre-menopausal women. We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug in women with HSDD., Patients and Methods: A systematic literature review from the PubMed database search was carried out until April 2016 using the following keywords: "HSDD", "flibanserin", "sexual desire" and "ransomised controlled trial"., Results: We found four randomized double-blind control studies and two meta-analyzes and literature reviews. For the comparison of flibanserin with placebo, the results were reported in standardized mean difference (SMD). Regarding the main criterion "Satisfactory Sexual Event" (SSE), SMD was ranged from 0.49 to 1 (P<0.05); "Desire Sexual Score" SMD was ranged from 1.63 to 2.20 (P<0.05). For the Female Sexual Function Index (FSFI) desire domain score SMD was ranged from 0.03 to 0.4 (P<0.05). Adverse effects were mostly minor: dizziness and drowsiness., Conclusion: Flibanserin showed a moderate benefit in terms of frequency of sex and patient satisfaction. The long-term safety of flibanserin is still poorly defined and scientific data concerning this drug are still few., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Purpose: Aortic stiffness is a functional and structural consequence of ageing and arteriosclerosis. Regional arterial stiffness can be easily evaluated using pOpmetre(®) (Axelife SAS, France). This new technique assesses the pulse wave transit time (TT) between the finger (TTf) and the toe (TTt). Based on height chart, regional pulse wave velocity (PWV) between the toe and the finger can be estimated (PWVtf). pOpscore(®) index is also calculated as the ratio between PWVtoe and PWVfinger and can be considered as a peripheral vascular stiffness index. The aim of the study was to evaluate the relationship between pOpmetre(®) indices and the presence of carotid plaques in a population with cardiovascular risk factors., Methods: In 77 consecutive patients recruited for a vascular screening for atherosclerosis (46 men aged 54 ± 2 years; 31 women aged 49 ± 3 years; ns), the difference between TTt and TTf (called Dt-f), the regional pulse wave velocity between the toe and the finger (PWVtf = constant × height/Dt-fm/s) and pOpscore(®) were measured by pOpmetre(®). Presence of carotid plaques was assessed using ultrasound imaging. The local aortic stiffness (AoStiff) was evaluated by the Physioflow(®) system., Results: No difference was found between patients with or without carotid plaques (n=25 versus 52) for Ankle-Brachial Pressure Index (ABPI: 1.15 ± 0.04 versus 1.12 ± 0.03), nor for diastolic or systolic blood pressure (87 ± 3 versus 82 ± 2; 137 ± 3 versus 132 ± 2 mmHg). The first group was older than the second (59 ± 2 versus 49 ± 2 years, P<0.002) with a larger intimae media thickness (0.69 ± 0.02 versus 0.63 ± 0.01 mm, P<0.004), a higher AoStiff (10.4 ± 0.7 versus 8.2 ± 0.5m/s, P<0.02), and PWVtf (14.3 ± 1.0 versus 10.7 ± 0.7 m/s, P<0.004) and a shorter Dt-f (57.9 ± 5.1 versus 73.5 ± 3.5 ms, P<0.01). PWVtf (r(2)=0.49, P<0.0001) and Dt-f (r(2)=0.54, P<0.0001) correlated with age. A significant difference in pOpscore(®) index was observed between both groups (1.51 ± 0.3 versus 1.41 ± 0.2, P<0.006)., Conclusion: Our results show a significant arterial stiffness indices measured by pOpmetre(®) in patients with and without carotid plaques., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Unlabelled: Various statistic predictive models have been developed to predict the status of the non-sentinel lymph nodes (NSLN) when the sentinel one was invaded by tumor cells in the case of breast invasive carcinoma. The objective of this study was to compare the accuracy of three of these statistic models: the MSKCC nomogram, the Tenon score and the MDA score. The study was conducted at Croix Rousse Hospital, Lyon, France., Objective: When sentinel lymph node is invaded by metastasis, complete lymph node dissection of the axilla can be avoided using statistic predictive models especially when talking about micrometastases and moreover about isolated tumor cells in the sentinel lymph node. Over the different existing models, we tested the three most used ones to determine the model that is most adapted to our everyday practice., Method: The study population consisted of 77 women with an invasive breast cancer treated by complete axillary lymph node dissection for metastatic sentinel lymph node. Over the nine models already published, we focused on three of them due to their ease to use as well as their good preliminary results: the Memorial Sloan-Kettering Cancer Center nomogram (MSKCC), the Tenon score and the M.D Anderson score (MDA). Different criteria are used by these models, but all of them take in consideration: tumor size, multifocality, tumor type, lymphovascular invasion, hormonal receptors, number of sentinel lymph node resected, degree of sentinel lymph node invasion (i.e. macrometastasis, micrometastasis or isolated tumor cells) and histologic method used to diagnose sentinel lymph node invasion. These scores are validated depending on their false negative ratio as well as the proportion of patient selected as having a low risk of non-sentinel lymph node invasion. The major criterion for the MSKCC score is the calibration that compares the predicted likelihood of invasion and the histologically proved one., Results: The rate of non-sentinel lymph node invasion was 37.6%. The discrimination of the three models was good with an AUC of 0.74 for both MSKCC nomogram and Tenon score and of 0.72% for MDA score. MSKCC nomogram was well calibrated (P=0.23). The false negative ratio was 0 (CI 95%: 0-18.1%) for MSKCC nomogram, 16.7% (CI 95%: 8.6%-27.8%) for Tenon score and 16% (CI 95%: 6.8-31%) for MDA score. The percentage of patients considered as having a low risk of invasion of the non-sentinel lymph node was 20.5% for MSKCC nomogram, 34.7% for MDA score and 47.4% for Tenon score., Conclusion: MSKCC nomogram seems to be the statistic model that is most adapted to the population we studied. To validate the Tenon and MDA score, we should have a most important population., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Structural and electronic properties of La(3+) immersed in bulk water have been assessed by means of density functional theory (DFT)-based Car-Parrinello molecular dynamics (CPMD) simulations. Correct structural properties, i.e., La(III)-water distances and La(III) coordination number, can be obtained within the framework of Car-Parrinello simulations providing that both the La pseudopotential and conditions of the dynamics (fictitious mass and time step) are carefully set up. DFT-MD explicitly treats electronic densities and is shown here to provide a theoretical justification to the necessity of including polarization when studying highly charged cations such as lanthanoids(III) with classical MD. La(3+) was found to strongly polarize the water molecules located in the first shell, giving rise to dipole moments about 0.5 D larger than those of bulk water molecules. Finally, analyzing Kohn-Sham orbitals, we found La(3+) empty 4f orbitals extremely compact and to a great extent uncoupled from the water conduction band, while the 5d empty orbitals exhibit mixing with unoccupied states of water.

Two-level fluctuations of the magnetization state of pseudo-spin-valve pillars Co(10 nm)/Cu(10 nm)/Co(30 nm) embedded in electrodeposited nanowires ( approximately 40 nm in diameter, 6000 nm in length) are triggered by spin-polarized currents of 10(7) A/cm(2) at room temperature. The statistical properties of the residence times in the parallel and antiparallel magnetization states reveal two effects with qualitatively different dependences on current intensity. The current appears to have the effect of a field determined as the bias field required to equalize these times. The bias field changes sign when the current polarity is reversed. At this field, the effect of a current density of 10(7) A/cm(2) is to lower the mean time for switching down to the microsecond range. This effect is independent of the sign of the current and is interpreted in terms of an effective temperature for the magnetization.

Objective: The aim of the study reported here was to set up a method for echocardiography (EC) and abdominal sonography and to obtain EC reference values for left ventricular (LV) morphology and function and sonographic abdominal aortic morphology, function, and flow values in conscious, unsedated Gottingen minipigs., Methods: Applying a standardized investigation procedure, the following parameters were measured by use of M-mode EC, color-coded Doppler imaging, and B-mode sonography, or were calculated, in 58 female minipigs: LV end-diastolic and end-systolic diameter, interventricular septum thickness, LV caudal wall thickness, LV end-diastolic volume and end-systolic volume, fractional shortening, ejection fraction, and percentage of thickening of interventricular septum and LV caudal wall. In addition, morphology, pulsatility, flow values, and flow patterns in the abdominal aorta were recorded or calculated during abdominal sonography and color-coded Doppler imaging., Results: Variable EC values were obtained due to individual variations of motor activity. Variation could be reduced by accustoming the animals to a standardized investigation procedure. Reference values could be obtained for EC, partially indicating clear correlation with body weight. Color-coded Doppler and Doppler spectra did not indicate flow disturbances in large arterial abdominal vessels., Conclusions: Results indicate that handling during EC and sonography can cause discomfort in unsedated minipigs that may interfere with recording of valid reference values for functional cardiac parameters in young animals. Accustoming the animals to a standardized investigation procedure reduces stress to a satisfactory level and enables data recording. Thus the minipig is considered suitable for assessment of cardiovascular parameters in experimental or toxicologic studies.

The hypothalamic nonapeptide arginine-vasopressin (AVP) exerts several distinct receptor-mediated actions on pituitary cells. Although hypothalamic AVP reaches the anterior pituitary via well-defined pathways, there is now accumulating evidence that AVP may also be produced endogenously in anterior pituitary cells. Using in situ hybridization, we demonstrate here the presence of AVP mRNA in the anterior pituitary of the rat. The observed grain density over pituitary cells was, however, greater than 10-fold lower than the one observed over AVP producing neurons present in the supraoptic and paraventricular nuclei of the hypothalamus. Immunoelectron microscopic analysis using two different AVP-specific antibodies revealed that the distribution of AVP-like immunoreactivity (AVP-LI) in the anterior pituitary is cell-specific. AVP-LI is most abundant in corticotrophs, followed by lactotrophs, gonadotrophs and thyrotrophs. On the other hand, there is complete absence of AVP-LI from somatotrophs. Interestingly, all pituitary cells in which AVP-LI is detected also represent potential target sites for AVP action. A minor fraction of AVP-LI was found to be membrane-associated and may originate, at least in part, from extrapituitary sources. This fraction likely represents receptor-bound peptide. The bulk of AVP-LI, however, was present in the cellular cytoplasm, not associated with any specific ultracellular structure. Specifically in corticotrophs, AVP-LI was excluded from secretory granules. However, our finding of AVP mRNA in anterior pituitary cells indicates that intracellular AVP-LI includes endogenously produced peptide, suggesting a paracrine and/or autocrine action.

Osteosarcoma-derived osteoblastic cells were exposed to 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) either to 0.001-1,000 nmol.l-1 for 4 days or to 10 nmol.-1 for 1-21 days. Between 0.01 and 10 nmol.l-1, a dose-dependent increase in alkaline phosphatase (AP) activity was found, which rose to a maximum level at 10 nmol.l-1 (+55%). At higher doses (100 and 1,000 nmol.l-1), 1,25(OH)2D3 induced a decrease in AP activity of 40%. After 1 day at 10 nmol.l-1 a slight increase in AP activity was noted (+20%) which augmented with the duration of exposure. This stimulatory effect was highest after 8 days (+130%). In contrast, after 15 and 21 days, AP activity decreased by 30%. Under 1,25(OH)2D3, microtubules were observed mainly in the perinuclear region.

Two experiments were performed using lactating cows fed various treated and non-treated commodities from AFB1 contaminated peanut cakes. Treatment with ammonia gas by an autoclaving process was used for detoxification. Two methods were used for AFM1 determination in every milk sample: a TLC procedure recognized by AOAC and IDF and an HPLC method with a detection limit of 0.100 and 0.010 microgram/l, respectively. In a first experiment, lactating cows were fed treated and untreated meals during periods separated by uncontaminated soya meals phases. The total excreted AFM1 was 2.6% of the total ingested AFB1 from untreated feed contaminated at 1100 micrograms/kg. During periods receiving treated meals in the diet, AFM1 contents in milk were below 0.1 microgram/l. However, by using AFM1 data obtained using the HPLC method, an AFM1/AFB1 ratio of 4.6% was found from treated feed contaminated at 40 micrograms AFB1/kg. In a second experiment, a herd of 50 lactating cows was used for a long term (16 months) feeding of mixed commodities containing 30% ammoniated peanut cakes. AFB1 residues in the treated diet were below 10 micrograms/kg, the EEC action level, and no AFM1 residue was found up to 0.1 microgram/l in collected milk throughout this experiment.