Longitudinal profiling of human androgenotes through single-cell analysis unveils paternal gene expression dynamics in early embryo development.

STUDY QUESTION: How do transcriptomics vary in haploid human androgenote embryos at single cell level in the first four cell cycles of embryo development? SUMMARY ANSWER: Gene expression peaks at the fourth cell cycle, however some androcytes exhibit unique transcriptional behaviors. WHAT IS KNOWN ALREADY: The developmental potential of an embryo is determined by the competence of the oocyte and the sperm. However, studies of the contribution of the paternal genome using pure haploid androgenotes are very scarce. STUDY DESIGN, SIZE, DURATION: This study was performed analyzing the single-cell transcriptomic sequencing of 38 androcytes obtained from 10 androgenote bioconstructs previously produced in vitro (de Castro et al., 2023). These results were analyzed through different bioinformatics software such as g: Profiler, GSEA, Cytoscape, and Reactome. PARTICIPANTS/MATERIALS, SETTING, METHODS: Single cell sequencing was used to obtain the transcriptomic profiles of the different androcytes. The results obtained were compared between the different cycles studied using the DESeq2 program and functional enrichment pathways using g: Profiler, Cytoscape, and Reactome. MAIN RESULTS AND THE ROLE OF CHANCE: A wave of paternally driven transcriptomic activation was found during the third-cell cycle, with 1128 upregulated and 225 downregulated genes and the fourth-cell cycle, with 1373 upregulated and 286 downregulated genes, compared to first-cell cycle androcytes. Differentially expressed routes related to cell differentiation, DNA-binding transcription, RNA biosynthesis and RNA polymerase II transcription regulatory complex, and cell death were found in the third and fourth with respect to the first-cell cycle. Conversely, in the fourth cell cycle, 153 downregulated and 332 upregulated genes were found compared with third cell cycle, associated with differentially expressed processes related to E-box binding and zinc finger protein 652 (ZNF652) transcription factor. Further, significant overexpression of LEUTX, PRAMEF1, DUXA, RFPL4A, TRIM43, and ZNF675 found in androgenotes, compared to biparental embryos, highlights the paternal contributions to zygote genome activation. LARGE SCALE DATA: All raw sequencing data are available through the Gene Expression Omnibus (GEO) under accessions number: GSE216501. LIMITATIONS, REASONS FOR CAUTION: Extrapolation of biological events from uniparental constructs to biparental embryos should be done with caution. Maternal and paternal genomes do not act independently of each other in a natural condition. The absence of one genome may affect gene transcription of the other. In this sense, the haploid condition of the bioconstructs could mask the transcriptomic patterns of the single cells. WIDER IMPLICATIONS OF THE FINDINGS: The results obtained demonstrated the level of involvement of the human paternal haploid genome in the early stages of embryo development as well as its evolution at the transcriptomic level, laying the groundwork for the use of these bioconstructs as reliable models to dispel doubts about the genetic role played by the paternal genome in the early cycles of embryo development. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Instituto de Salud Carlos III (ISCIII) through the project 'PI22/00924', co-funded by European Regional Development Fund (ERDF); 'A way to make Europe'. F.D. was supported by the Spanish Ministry of Economy and Competitiveness through the Miguel Servet program (CPII018/00002). M.J.E. was supported by Instituto de Salud Carlos III (PI19/00577 [M.J.E.]) and FI20/00086. P.dC. was supported by a predoctoral grant for training in research into health (PFIS PI19/00577) from the Instituto de Salud Carlos III. All authors declare having no conflict of interest with regard to this trial.

[An unusual cause of a decline in general health in a very old person]. / Une cause inhabituelle d'altération de l'état général chez une personne très âgée.

Humans are accidental intermediate hosts and a dead-end for the echinococcosis parasite. No cases of hydatid echinococcosis (hydatid cyst) have ever been described in a French-born very elderly person, who has never been out of France. We report the case of a 90-year-old man hospitalised following a decline in his general health and the discovery of a liver mass on the CT-scan. The abdominal palpation was painless, and no mass was felt. Biological tests revealed hypereosinophilia, a mild inflammatory syndrome, a slight increase in the immunoglobulin E level, and positive serology for Echinococcus granulosus. A diagnosis of hydatid echinococcosis due to Echinococcus granulosus was made given the liver mass on the CT-scan, the positive serology and the hypereosinophilia. Management consisted of watch and wait. This observation is interesting because it was a case of an autochthonous hydatid cyst of an unexpected discovery in a very elderly patient. Indeed, even though the discovery was classical, the clinical presentation was singular because of the context.

L'être humain est un hôte intermédiaire accidentel et une impasse parasitaire pour l'échinococcose. Aucun cas de kyste hydatique (échinococcose hydatique) n'a été décrit chez une personne très âgée née en France et ne l'ayant jamais quittée. Nous rapportons ici le cas d'un patient âgé de 90 ans hospitalisé pour altération de l'état général et découverte d'une masse hépatique à la tomodensitométrie. La palpation abdominale était indolore sans masse perçue. Le bilan biologique révélait une hyperéosinophilie, un discret syndrome inflammatoire, une légère augmentation du taux d'immunoglobuline E et une sérologie de l'Echinococcus granulosus positive. Le diagnostic d'échinococcose hydatique (kyste hydatique) due à Echinococcus granulosus fut alors posé, compte tenu de la masse hépatique découverte à la tomodensitométrie, de la sérologie positive et de l'hyperéosinophilie. La prise en charge a consisté en une attitude «watch and wait¼. Cette observation est intéressante car il s'agissait d'un cas de kyste hydatique autochtone de découverte fortuite chez un patient très âgé. En effet, même si le mode de découverte était classique, le tableau clinique était singulier en raison du contexte.

Aharonov-Bohm Oscillations in Minimally Twisted Bilayer Graphene.

We investigate transport in the network of valley Hall states that emerges in minimally twisted bilayer graphene under interlayer bias. To this aim, we construct a scattering theory that captures the network physics. In the absence of forward scattering, symmetries constrain the network model to a single parameter that interpolates between one-dimensional chiral zigzag modes and pseudo-Landau levels. Moreover, we show how the coupling of zigzag modes affects magnetotransport. In particular, we find that scattering between parallel zigzag channels gives rise to Aharonov-Bohm oscillations that are robust against temperature, while coupling between zigzag modes propagating in different directions leads to Shubnikov-de Haas oscillations that are smeared out at finite temperature.

Inhibition of KIF20A by BKS0349 reduces endometriotic lesions in a xenograft mouse model.

Several studies have suggested a possible etiological association between ovarian endometriosis and ovarian cancer. Evidence has shown that KIF20A overexpression might confer a malignant phenotype to ovarian tumors by promoting proliferation and inhibiting apoptosis. However, no data about the role of KIF20A in endometriosis have been described. In this study, the human endometrium (n = 4) was transfected by mCherry adenovirus and intraperitoneally implanted in mice. Subsequently, mice were divided in three groups (n = 8/group) that were treated with Vehicle, BKS0349 (KIF20A-antagonist) or cabergoline (dopamine receptor agonist) for 21 days. mCherry-labeled endometriotic lesions were monitored over time using the IVIS Imaging System. Mice were sacrificed 72 h after the last administration; proliferation was evaluated by immunohistochemistry and apoptosis by TUNEL. CCND1 gene expression (G1 phase-related gene) was measured by qRT-PCR. A significant reduction in mCherry-fluorescent signal was observed in the BKS0349 group after treatment ended (D24) compared with D0 (P-value = 0.0313). Moreover, the mCherry signal on D24 showed a significant decrease in the BKS0349 group compared with controls (P-value = 0.0303), along with significant size reduction of endometriotic lesions observed in the BKS0349 group compared with control on D24 (P-value = 0.0006). Functional studies showed a significant reduction in proliferating cells in the BKS0349-treated group compared with controls (P-value = 0.0082). In addition, CCND1 expression was decreased in the BKS0349 group compared with control (P-value = 0.049) at D24 and a significant increase in apoptotic cells among endometriotic lesions in BKS0349-treated mice was observed compared with control (P-value = 0.0317). Based on these findings, we concluded that BKS0349 induces apoptosis and inhibits cell proliferation, reducing endometriotic lesion size and suggesting KIF20A inhibition by BKS0349 as a novel therapeutic treatment for endometriosis.

Toxicity assessment of cobalt ferrite nanoparticles on wheat plants.

Cobalt ferrite nanoparticles (NPs) have received increasing attention due to their widespread therapeutic and agricultural applicability. In the environmental field, dry powder- and ferrofluid-suspended cobalt ferrite NPs were found to be useful for removing heavy metals and metalloids from water, while diluted suspensions of cobalt ferrite NP have been promisingly applied in medicine. However, the potential toxicological implications of widespread exposure are still unknown. Since cobalt ferrite NPs are considered residual wastes of environmental or medical applications, plants may serve as a point-of-entry for engineered nanomaterials as a result of consumption of these plants. Thus, the aim of this study was to assess the effects of dry powder and fresh cobalt ferrite NP on wheat plants. Seven-day assays were conducted, using quartz sand as the plant growth substrate. The toxicity end points measured were seed germination, root and shoot lengths, total cobalt (Co) and iron (Fe) accumulation, photosynthetic pigment production, protein (PRT) production, and activities of catalase (CAT), ascorbate peroxidase (APX), and guaiacol peroxidase (GPX). Increasing total Co and Fe in plant tissues indicated that wheat plants were exposed to cobalt ferrite NP. Seed germination and shoot length were not sufficiently sensitive toxicity end points. The effective concentration (EC50) that diminished root length of plants by 50% was 1963 mg/kg for fresh ferrite NPs and 5023 mg/kg for powder ferrite NP. Hence, fresh ferrite NPs were more toxic than powder NP. Plant stress was indicated by a significant decrease in photosynthetic pigments. CAT, APX, and GPX antioxidant enzymatic activity suggested the generation of reactive oxygen species and oxidative damage induced by cobalt ferrite NP. More studies are thus necessary to determine whether the benefits of using these NPs outweigh the risks.

How might recharge change under projected climate change in western US?

Although groundwater is a major resource of water in the western US, little research has been done on the impacts of climate change on groundwater storage and recharge in the West. Here we assess the impact of projected changes in climate on groundwater recharge in the near (2021-2050) and far (2071-2100) future across the western US. Recharge is expected to decrease slightly (highly certain) in the West (-1.6%) and Southwest (-2.9%) regions in the near future and decrease considerably (highly certain) in the South region (-10.6%) in the far future. The Northern Rockies region is expected to get more recharge (highly certain) in both the near (+5.0%) and far (+9.0%) future. In general, southern portions of the western US are expected to get less recharge in the future and northern portions will get more. This study also shows that climate change interacts with land surface properties to affect the amount of recharge that occurs in the future.

Magnetic Field Tuning and Quantum Interference in a Cooper Pair Splitter.

Cooper pair splitting (CPS) is a process in which the electrons of the naturally occurring spin-singlet pairs in a superconductor are spatially separated using two quantum dots. Here, we investigate the evolution of the conductance correlations in an InAs CPS device in the presence of an external magnetic field. In our experiments the gate dependence of the signal that depends on both quantum dots continuously evolves from a slightly asymmetric Lorentzian to a strongly asymmetric Fano-type resonance with increasing field. These experiments can be understood in a simple three-site model, which shows that the nonlocal CPS leads to symmetric line shapes, while the local transport processes can exhibit an asymmetric shape due to quantum interference. These findings demonstrate that the electrons from a Cooper pair splitter can propagate coherently after their emission from the superconductor and how a magnetic field can be used to optimize the performance of a CPS device. In addition, the model calculations suggest that the estimate of the CPS efficiency in the experiments is a lower bound for the actual efficiency.

[Multimodal neuromonitoring in traumatic brain injury: contribution of PTiO2]. / Neuromonitorización multimodal en el TCE: aportación de la PTiO2.

The main goal of exhaustively monitoring neurocritical patients is to avoid secondary injury. In the last few years we have witnessed an increase in brain monitoring tools, beyond the checking of intracranial and brain perfusion pressures. These widely used systems offer valuable but possibly insufficient information. Awareness and correction of brain hypoxia is a useful and interesting measure, not only for diagnostic purposes but also when deciding treatment, and to predict an outcome. In this context, it would be of great interest to use all the information gathered from brain oxygenation monitoring systems in conjunction with other available multimodal monitoring devices, in order to offer individualized treatment for each patient.

Mosaic results after preimplantation genetic testing for aneuploidy may be accompanied by changes in global gene expression.

Aneuploidy in preimplantation embryos is a major cause of human reproductive failure. Unlike uniformly aneuploid embryos, embryos diagnosed as diploid-aneuploid mosaics after preimplantation genetic testing for aneuploidy (PGT-A) can develop into healthy infants. However, the reason why these embryos achieve full reproductive competence needs further research. Current RNA sequencing techniques allow for the investigation of the human preimplantation transcriptome, providing new insights into the molecular mechanisms of embryo development. In this prospective study, using euploid embryo gene expression as a control, we compared the transcriptome profiles of inner cell mass and trophectoderm samples from blastocysts with different levels of chromosomal mosaicism. A total of 25 samples were analyzed from 14 blastocysts with previous PGT-A diagnosis, including five low-level mosaic embryos and four high-level mosaic embryos. Global gene expression profiles visualized in cluster heatmaps were correlated with the original PGT-A diagnosis. In addition, gene expression distance based on the number of differentially expressed genes increased with the mosaic level, compared to euploid controls. Pathways involving apoptosis, mitosis, protein degradation, metabolism, and mitochondrial energy production were among the most deregulated within mosaic embryos. Retrospective analysis of the duration of blastomere cell cycles in mosaic embryos revealed several mitotic delays compared to euploid controls, providing additional evidence of the mosaic status. Overall, these findings suggest that embryos with mosaic results are not simply a misdiagnosis by-product, but may also have a genuine molecular identity that is compatible with their reproductive potential.

Tb3+-Tb3+ cross-relaxation study under novel experimental technique: Simultaneous laser excitation at UV-Vis.

Tb3+ doped GeO2-Na2O glasses have been fabricated by conventional melt quenching technique using 0.3, 1, 3, and 5 %mol of terbium ions. The optical properties were studied by means of steady-state photoluminescence (excitation and emission spectra), and emission decay time. Under excitation of 355 nm and as the concentration of dopant increases, the glasses show an enhancement of the emission intensity from 5D4 level accompanied by a decrease on the emission intensity from 5D3 level. This phenomenon can be attributed to an energy transfer process that occurs through cross-relaxation mechanisms between Tb3+ ions. The aim of this study is to report an experimental technique to study the cross-relaxation of 5D3 level decay curves of Tb3+ ions under simultaneous temporal and spatial pulsed excitation using UV and visible light (355 nm + 488 nm), allowing to limit the occurrence of cross-relaxation mechanisms and increase luminescent efficiency. Upon simultaneous UV + Vis excitation, the emission from 5D3 level in enhanced, as the energy of the 488 nm pulse is increased. Additionally, the energy transfer efficiency between Tb3+ ions was analyzed with the Inokuti-Hirayama (IH) model, as function of the excitation pulse energy at 488 nm, keeping fixed the energy of the 355 nm pulse, determining a dipole-dipole interaction as the dominant interaction mechanism.

Effective lifting of the topological protection of quantum spin Hall edge states by edge coupling.

The scientific interest in two-dimensional topological insulators (2D TIs) is currently shifting from a more fundamental perspective to the exploration and design of novel functionalities. Key concepts for the use of 2D TIs in spintronics are based on the topological protection and spin-momentum locking of their helical edge states. In this study we present experimental evidence that topological protection can be (partially) lifted by pairwise coupling of 2D TI edges in close proximity. Using direct wave function mapping via scanning tunneling microscopy/spectroscopy (STM/STS) we compare isolated and coupled topological edges in the 2D TI bismuthene. The latter situation is realized by natural lattice line defects and reveals distinct quasi-particle interference (QPI) patterns, identified as electronic Fabry-Pérot resonator modes. In contrast, free edges show no sign of any single-particle backscattering. These results pave the way for novel device concepts based on active control of topological protection through inter-edge hybridization for, e.g., electronic Fabry-Pérot interferometry.

A frequency comb stabilized Ti:Sa laser as a self-reference for ion-trap experiments with a 40Ca+ ion.

In this study, we report on the stabilization of a continuous-wave Ti:Sa laser to an optical frequency comb. The laser is emitting at 866 nm to address one of the transitions required for Doppler cooling of a single 40Ca+ ion in a linear Paul trap (2D3/2 ↔P1/22). The stabilized Ti:Sa laser is utilized to calibrate an ultra-accurate wavelength meter. We certify this self-reference laser source by comparing the results from monitoring the laser-cooled 40Ca+ ion in the linear Paul trap, with those obtained when a HeNe laser is used for calibration. The use of this self-reference is compatible with the simultaneous use of the comb for precision spectroscopy in the same ion-trap experiment.

[Recommendations for the use of neurophysiological techniques in the diagnosis of brain death from the Clinical Neurophysiology Society of the Communities of Valencia and Murcia]. / Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia.

In Spain organ transplantation constitutes one of the greatest challenges and teamwork of hospital centres. It is estimated that in the year 2020 Spain contributed 19% of all donors to the European Union. The confirmatory support diagnosis recommends by law some complementary techniques in certain cases, including neurophysiological techniques, especially the use of electroencephalogram and evoked potentials. These cases require the clinical neurophysiologist to make the right clinical and technical decisions for the correct performance and interpretation of the same. To date, there is no national consensus on the performance of these techniques. Updated bibliographic review on neurophysiological techniques (electroencephalogram and evoked potentials). Analysis by Delphi method and expert judgment of the working group of the Clinical Neurophysiology Society of the Communities of Valencia and Murcia. Neurophysiological techniques can be a support in the diagnosis of encephalic death, both confirmatory and to shorten observation times. In order to perform them, minimum technical standards are required to allow optimal performance of the studies, especially taking into account medication, hemodynamic situation, absence of hypothermia, and age group. We present the first guide in Spanish elaborated by the Society of Neurophysiology of the Communities of Valencia and Murcia for the performance in our hospitals of neurophysiological techniques in the diagnosis of brain death.

TITLE: Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia.En España, el trasplante de órganos constituye uno de los mayores retos y trabajo en equipo de los centros hospitalarios. Se estima que en 2020 España aportó a la Unión Europea el 19% de la totalidad de los donantes. El diagnóstico de apoyo confirmatorio recomienda por ley algunas técnicas complementarias en determinados casos, entre ellas las técnicas neurofisiológicas, en especial el uso del electroencefalograma y los potenciales evocados. Estos casos plantean al neurofisiólogo clínico la toma acertada de decisiones tanto clínicas como técnicas para su correcta realización e interpretación. Hasta ahora no existe a nivel nacional un consenso de realización de estas técnicas. Es una revisión bibliográfica actualizada sobre las técnicas neurofisiológicas (electroencefalograma y potenciales evocados), con análisis mediante método Delphi y juicio de expertos del grupo de trabajo de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia. Las técnicas neurofisiológicas permiten ser un apoyo en el diagnóstico de muerte encefálica, tanto de forma confirmatoria como para acortar tiempos de observación. Para su realización se precisan unos mínimos estándares técnicos que permitan realizar de forma óptima los estudios. Especialmente hay que tener en cuenta la medicación, la situación hemodinámica, la ausencia de hipotermia y el grupo de edad. Presentamos la primera guía en castellano elaborada por la Sociedad de Neurofisiología de las Comunidades de Valencia y Murcia para la realización en nuestros hospitales de las técnicas neurofisiológicas en el diagnóstico de muerte encefálica.

ADENI-UCI study: Analysis of non-income decisions in ICU as a measure of limitation of life support treatments.

OBJECTIVE: To analyze the variables associated with ICU refusal decisions as a life support treatment limitation measure. DESIGN: Prospective, multicentrico. SCOPE: 62 ICU from Spain between February 2018 and March 2019. PATIENTS: Over 18 years of age who were denied entry into ICU as a life support treatment limitation measure. INTERVENTIONS: None. MAIN INTEREST VARIABLES: Patient comorities, functional situation as measured by the KNAUS and Karnosfky scale; predicted scales of Lee and Charlson; severity of the sick person measured by the APACHE II and SOFA scales, which justifies the decision-making, a person to whom the information is transmitted; date of discharge or in-hospital death, destination for hospital discharge. RESULTS: A total of 2312 non-income decisions were recorded as an LTSV measure of which 2284 were analyzed. The main reason for consultation was respiratory failure (1080 [47.29%]). The poor estimated quality of life of the sick (1417 [62.04%]), the presence of a severe chronic disease (1367 [59.85%]) and the prior functional limitation of patients (1270 [55.60%]) were the main reasons for denying admission. The in-hospital mortality rate was 60.33%. The futility of treatment was found as a risk factor associated with mortality (OR: 3.23; IC95%: 2.62-3.99). CONCLUSIONS: Decisions to limit ICU entry as an LTSV measure are based on the same reasons as decisions made within the ICU. The futility valued by the intensivist is adequately related to the final result of death.

Site-specific recognition of SARS-CoV-2 nsp1 protein with a tailored titanium dioxide nanoparticle.

The ongoing world-wide Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) pandemic shows the need for new sensing and therapeutic means against the CoV viruses. The SARS-CoV-2 nsp1 protein is important, both for replication and pathogenesis, making it an attractive target for intervention. In recent years nanoparticles have been shown to interact with peptides, ranging in size from single amino acids up to proteins. These nanoparticles can be tailor-made with specific functions and properties including bioavailability. To the best of our knowledge, in this study we show for the first time that a tailored titanium oxide nanoparticle interacts specifically with a unique site of the full-length SARS-CoV-2 nsp1 protein. This can be developed potentially into a tool for selective control of viral protein functions.

Drug-drug interactions between treatment specific pharmacotherapy and concomitant medication in patients with COVID-19 in the first wave in Spain.

Primary aim was to assess prevalence and severity of potential and real drug-drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) ('potential interactions') and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02-1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12-1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.

Proteomics of embryonic implantation.

Implantation is a complex process involving an intricate cascade of molecular interactions between the implanting blastocyst and the receptive endometrium. The molecular basis of endometrial receptivity and the mechanisms by which the blastocyst first adheres to the luminal epithelium and then penetrates into the stroma are only just beginning to be resolved. Advances in "omics" technologies, particularly proteomics and metabolomics, are set to have a major impact on the development of this field. In the wake of this information, novel targets for contraceptive intervention may become apparent.

Copper and lead exposures disturb reproductive features of primary endometrial stromal and epithelial cells.

This study investigates if Cu and Pb act as endocrine disruptors affecting endometrial cells. Primary EnSCs and EnECs were exposed to Cu (0, 50, 100 and 200 µM) or Pb (0, 30, 100 and 500 µM) and assessed for viability, decidualization, apoptosis and proliferation on EnSCs, and wound healing and adhesion capabilities on EnECs. Cu exposure decreased significantly cell viability in a dose-dependent manner. Cu and Pb negatively affected in vitro decidualization, showing a significant decrease in PRL secretion. HOXA10 and ERα mRNA levels significantly decreased in decidualized cells (dEnSCs) exposed to Cu. Cu and Pb decreased adhesion and regeneration capability in EnEC. This study reveals that Cu and Pb could negatively affect endometrial functionality, compromising the decidualization process and disrupting endometrial regeneration and embryo adhesion. Therefore, special care should be taken considering heavy metals exposure if pregnancy is being pursued.

ADENI-UCI Study: Analysis of non-income decisions in ICU as a measure of limitation of life support treatments. / Estudio ADENI-UCI: Análisis de las decisiones de no ingreso en UCI como medida de limitación de los tratamientos de soporte vital.

OBJECTIVE: To analyze the variables associated with ICU refusal decisions as a life support treatment limitation measure. DESIGN: Prospective, multicentrico SCOPE: 62 ICU from Spain between February 2018 and March 2019. PATIENTS: Over 18 years of age who were denied entry into ICU as a life support treatment limitation measure. INTERVENTIONS: None. MAIN INTEREST VARIABLES: Patient comorities, functional situation as measured by the KNAUS and Karnosfky scale; predicted scales of Lee and Charlson; severity of the sick person measured by the APACHE II and SOFA scales, which justifies the decision-making, a person to whom the information is transmitted; date of discharge or in-hospital death, destination for hospital discharge. RESULTS: A total of 2312 non-income decisions were recorded as an LTSV measure of which 2284 were analyzed. The main reason for consultation was respiratory failure (1080 [47.29%]). The poor estimated quality of life of the sick (1417 [62.04%]), the presence of a severe chronic disease (1367 [59.85%]) and the prior functional limitation of patients (1270 [55.60%]) were the main reasons for denying admission. The in-hospital mortality rate was 60.33%. The futility of treatment was found as a risk factor associated with mortality (OR: 3.23; IC95%: 2.62-3.99). CONCLUSIONS: Decisions to limit ICU entry as an LTSV measure are based on the same reasons as decisions made within the ICU. The futility valued by the intensivist is adequately related to the final result of death.