1st INEXO Symposium: Alternative models in vitro, ex ovo and organisms: From research to applications in pathologies and aging

International audience123 gation and subsequent differentiation into complex tissue-like structures with reproducible ratios of neurons, astrocytes and oligodendrocytes. The generated neurons elicit spontaneous calcium transients and stimuli-induced neurotransmitter release. Whole-cell current-and-voltage clamp recordings show polarized neurons and voltage-dependent ion currents. Differentiated glial cells present astrocytic functions. Moreover, expression of genes involved in synaptic and ion transport machinery and the accumulation of neural proteoglycans suggests that this 3D differentiation strategy mimics the neural tissue microenvironment better than other differentiation methods. These models have applications as tools for preclinical assessment and in disease modelling. In the next session on reconstituted tissues and 3D bioprint-ing, Dr Christian Pellevoisin (Episkin Academy, Lyon, France) spoke about reconstructed skin, which is a powerful and highly versatile technology already used at all stages of cosmetic product development (toxicology, UV sensitivity, skin allergy, skin aging, skin microbiome, etc). The ability to reproduce several functions of human skin in vitro broadens the scope for industrial applications. He demonstrated that it is now possible to predict positive or negative effects of cosmetics early in their development process using in vitro skin models instead of animal testing. Reconstructed human skin is also used for screening and assessing the efficacy of new active ingredients, deciphering their mechanism of action, and optimizing the composition of formulations

Acral Acquired Cutis Laxa Associated with IgA Multiple Myeloma, Joint Hyper laxity and Urticarial Neutrophilic Dermatosis

Peer reviewe

Mitochondrial DNA parameters in blood of infants receiving lopinavir/ritonavir or lamivudine prophylaxis to prevent breastfeeding transmission of HIV-1

Children who are human immunodeficiency virus (HIV)-exposed but uninfected (CHEU) accumulate maternal HIV and antiretroviral exposures through pregnancy, postnatal prophylaxis, and breastfeeding. Here, we compared the dynamics of mitochondrial DNA (mtDNA) parameters in African breastfed CHEU receiving lopinavir/ritonavir (LPV/r) or lamivudine (3TC) pre-exposure prophylaxis during the first year of life. The number of mtDNA copies per cell (MCN) and the proportion of deleted mtDNA (MDD) were assessed at day 7 and at week 50 post-delivery (PrEP group). mtDNA depletion was defined as a 50% or more decrease from the initial value, and mtDNA deletions was the detection of mtDNA molecules with large DNA fragment loss. We also performed a sub-analysis with CHEU who did not receive a prophylactic treatment in South Africa (control group). From day seven to week 50, MCN decreased with a median of 41.7% (interquartile range, IQR: 12.1; 64.4) in the PrEP group. The proportion of children with mtDNA depletion was not significantly different between the two prophylactic regimens. Poisson regressions showed that LPV/r and 3TC were associated with mtDNA depletion (reference: control group; LPV/r: PR = 1.75 (CI95%: 1.15–2.68), p < 0.01; 3TC: PR = 1.54 (CI95%: 1.00–2.37), p = 0.05). Moreover, the proportion of children with MDD was unexpectedly high before randomisation in both groups. Long-term health impacts of these mitochondrial DNA parameters should be investigated further for both CHEU and HIV-infected children receiving LPV/r- or 3TC- based regimens.http://www.mdpi.com/journal/jcmpm2021Paediatrics and Child Healt

Eliminating HIV transmission through breast milk from women taking antiretroviral drugs

Mothers taking antiretroviral drugs with low plasma viral loads may still transmit HIV to their breastfeeding children. Given the widely acknowledged benefits of breastfeeding, eliminating the risk of vertical transmission of HIV through breast milk must be a priority.https://bjsm.bmj.comam2022Paediatrics and Child Healt

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe