Increased glutamatergic neurotransmission between the retinohypothalamic tract and the suprachiasmatic nucleus of old mice.

Circadian rhythms synchronize to light through the retinohypothalamic tract (RHT), which is a bundle of axons coming from melanopsin retinal ganglion cells, whose synaptic terminals release glutamate to the ventral suprachiasmatic nucleus (SCN). Activation of AMPA-kainate and NMDA postsynaptic receptors elicits the increase in intracellular calcium required for triggering the signaling cascade that ends in phase shifts. During aging, there is a decline in the synchronization of circadian rhythms to light. With electrophysiological (whole-cell patch-clamp) and immunohistochemical assays, in this work, we studied pre- and postsynaptic properties between the RHT and ventral SCN neurons in young adult (P90-120) and old (P540-650) C57BL/6J mice. Incremental stimulation intensities (applied on the optic chiasm) induced much lesser AMPA-kainate postsynaptic responses in old animals, implying a lower recruitment of RHT fibers. Conversely, a higher proportion of old SCN neurons exhibited synaptic facilitation, and variance-mean analysis indicated an increase in the probability of release in RHT terminals. Moreover, both spontaneous and miniature postsynaptic events displayed larger amplitudes in neurons from aged mice, whereas analysis of the NMDA and AMPA-kainate components (evoked by RHT electrical stimulation) disclosed no difference between the two ages studied. Immunohistochemistry revealed a bigger size in the puncta of vGluT2, GluN2B, and GluN2A of elderly animals, and the number of immunopositive particles was increased, but that of PSD-95 was reduced. All these synaptic adaptations could be part of compensatory mechanisms in the glutamatergic signaling to ameliorate the loss of RHT terminals in old animals.

ß

For the first time, the (d,^{2}He) reaction was successfully used in inverse kinematics to extract the Gamow-Teller transition strength in the ß^{+} direction from an unstable nucleus. The new technique was made possible by the use of an active-target time-projection chamber and a magnetic spectrometer, and opens a path to addressing a range of scientific challenges, including in astrophysics and neutrino physics. In this Letter, the nucleus studied was ^{14}O, and the Gamow-Teller transition strength to ^{14}N was extracted up to an excitation energy of 22 MeV. The data were compared to shell-model and state-of-the-art coupled-cluster calculations. Shell-model calculations reproduce the measured Gamow-Teller strength distribution up to about 15 MeV reasonably well, after the application of a phenomenological quenching factor. In a significant step forward to better understand this quenching, the coupled-cluster calculation reproduces the full strength distribution well without such quenching, owing to the large model space, the inclusion of strong correlations, and the coupling of the weak interaction to two nucleons through two-body currents.

Developmental light deprivation transiently reduces the expression of vGluT2 and GluN2B in the rat ventral suprachiasmatic nucleus.

The suprachiasmatic nucleus (SCN) is the most important circadian clock in mammals. The SCN synchronizes to environmental light via the retinohypothalamic tract (RHT), which is an axon cluster derived from melanopsin-expressing intrinsic photosensitive retinal ganglion cells. Investigations on the development of the nonimage-forming pathway and the RHT are scarce. Previous studies imply that light stimulation during postnatal development is not needed to make the RHT functional at adult stages. Here, we examined the effects of light deprivation (i.e., constant darkness (DD) rearing) during postnatal development on the expression in the ventral SCN of two crucial proteins for the synchronization of circadian rhythms to light: the presynaptic vesicular glutamate transporter type 2 (vGluT2) and the GluN2B subunit of the postsynaptic NMDA receptor. We found that animals submitted to DD conditions exhibited a transitory reduction in the expression of vGluT2 (at P12-19) and of GluN2B (at P7-9) that was compensated at older stages. These findings support the hypothesis that visual stimulation during early ages is not decisive for normal development of the RHT-SCN pathway.

Multigene phylogeny of the order Physarales (Myxomycetes, Amoebozoa): shedding light on the dark-spored clade.

The class Myxomycetes consists of free-living protists characterised by their complex life cycle, which includes both microscopic (amoebae, flagellates and cists) and macroscopic stages (spore-bearing fruiting bodies, sclerotia, and plasmodia). Within it, the order Physarales, with more than 450 recognised species, constitutes the largest group. Although previous studies have shown the polyphyly of some of the traditionally accepted genera, its internal phylogenetic relationships have remained uncertain so far, and together with the lack of data for some key species, it prevented any taxonomic and nomenclatural revisions. We have compiled a substantially expanded dataset in terms of both taxon sampling and molecular data, including most of the genera described to date and four unlinked DNA regions, for which we provide partial sequences: nSSU, EF-1α, α-Tub, and mtSSU, analysed through maximum likelihood and Bayesian methods. Our results confirm that the family Didymiaceae is paraphyletic to the rest of Physarales. Within Didymiaceae s.lat., the recent reinstatement of the genus Polyschismium for most species traditionally ascribed to Lepidoderma, except for the type (Ronikier et al. 2022), is further supported here, as well as the definite inclusion of the genus Mucilago in Didymium and Lepidoderma s.str. (L. tigrinum) in Diderma (Prikhodko et al. 2023). Additionally, the genus Diachea is redefined to include some species previously treated in Physaraceae (Craterium spp. with true columella). Within the monophyletic family Physaraceae, most genera are recovered as polyphyletic, suggesting that they should be no longer accepted as currently defined. However, the lack of resolution of some relationships within Physaraceae prevents us from resuscitating or creating several new genera to mitigate polyphyly. Among the well-defined groups with clear molecular signatures, we propose two taxonomic and nomenclatural changes at generic level: 1) a new genus, Nannengaella, is proposed for a major clade containing Physarum globuliferum and other species with heavily calcified sporophores and, often, a true calcareous columella; 2) Lignydium is resurrected for the clade containing Fuligo muscorum. Additionally, Trichamphora is suggested as the correct name for the clade containing Physarum pezizoideum. The taxonomy and nomenclature of some provisional genera, currently synonymous with Fuligo and Physarum, are disentangled, and we provide a comprehensive and updated nomenclatural conspectus that can be used when better resolved phylogenies are obtained. In total, 22 new combinations are proposed in different genera. A provisional key to the genera of the order is also provided. Citation: García-Martín JM, Zamora JC, Lado C. 2023. Multigene phylogeny of the order Physarales (Myxomycetes, Amoebozoa): shedding light on the dark-spored clade. Persoonia 51: 89-124. doi: 10.3767/persoonia.2023.51.02.

Novel Roles of the N1 Loop and N4 Alpha-Helical Region of the Nipah Virus Fusion Glycoprotein in Modulating Early and Late Steps of the Membrane Fusion Cascade.

Nipah virus (NiV) is a zoonotic bat henipavirus in the family Paramyxoviridae NiV is deadly to humans, infecting host cells by direct fusion of the viral and host cell plasma membranes. This membrane fusion process is coordinated by the receptor-binding attachment (G) and fusion (F) glycoproteins. Upon G-receptor binding, F fuses membranes via a cascade that sequentially involves F-triggering, fusion pore formation, and viral or genome entry into cells. Using NiV as an important paramyxoviral model, we identified two novel regions in F that modulate the membrane fusion cascade. For paramyxoviruses and other viral families with class I fusion proteins, the heptad repeat 1 (HR1) and HR2 regions in the fusion protein prefusion conformation bind to form a six-helix bundle in the postfusion conformation. Here, structural comparisons between the F prefusion and postfusion conformations revealed that a short loop region (N1) undergoes dramatic spatial reorganization and a short alpha helix (N4) undergoes secondary structural changes. The roles of the N1 and N4 regions during the membrane fusion cascade, however, remain unknown for henipaviruses and paramyxoviruses. By performing alanine scanning mutagenesis and various functional analyses, we report that specific residues within these regions alter various steps in the membrane fusion cascade. While the N1 region affects early F-triggering, the N4 region affects F-triggering, F thermostability, and extensive fusion pore expansion during syncytium formation, also uncovering a link between F-G interactions and F-triggering. These novel mechanistic roles expand our understanding of henipaviral and paramyxoviral F-triggering, viral entry, and cell-cell fusion (syncytia), a pathognomonic feature of paramyxoviral infections.IMPORTANCE Henipaviruses infect bats, agriculturally important animals, and humans, with high mortality rates approaching ∼75% in humans. Known human outbreaks have been concentrated in Southeast Asia and Australia. Furthermore, about 20 new henipaviral species have been recently discovered in bats, with geographical spans in Asia, Africa, and South America. The development of antiviral therapeutics requires a thorough understanding of the mechanism of viral entry into host cells. In this study, we discovered novel roles of two regions within the fusion protein of the deadly henipavirus NiV. Such roles were in allowing viral entry into host cells and cell-cell fusion, a pathological hallmark of this and other paramyxoviruses. These novel roles were in the previously undescribed N1 and N4 regions within the fusion protein, modulating early and late steps of these important processes of viral infection and henipaviral disease. Notably, this knowledge may apply to other henipaviruses and more broadly to other paramyxoviruses.

Roles of Cholesterol in Early and Late Steps of the Nipah Virus Membrane Fusion Cascade.

Cholesterol has been implicated in various viral life cycle steps for different enveloped viruses, including viral entry into host cells, cell-cell fusion, and viral budding from infected cells. Enveloped viruses acquire their membranes from their host cells. Although cholesterol has been associated with the binding and entry of various enveloped viruses into cells, cholesterol's exact function in the viral-cell membrane fusion process remains largely elusive, particularly for the paramyxoviruses. Furthermore, paramyxoviral fusion occurs at the host cell membrane and is essential for both virus entry (virus-cell fusion) and syncytium formation (cell-cell fusion), central to viral pathogenicity. Nipah virus (NiV) is a deadly member of the Paramyxoviridae family, which also includes Hendra, measles, mumps, human parainfluenza, and various veterinary viruses. The zoonotic NiV causes severe encephalitis, vasculopathy, and respiratory symptoms, leading to a high mortality rate in humans. We used NiV as a model to study the role of membrane cholesterol in paramyxoviral membrane fusion. We used a combination of methyl-beta cyclodextrin (MßCD), lovastatin, and cholesterol to deplete or enrich cell membrane cholesterol outside cytotoxic concentrations. We found that the levels of cellular membrane cholesterol directly correlated with the levels of cell-cell fusion induced. These phenotypes were paralleled using NiV/vesicular stomatitis virus (VSV)-pseudotyped viral infection assays. Remarkably, our mechanistic studies revealed that cholesterol reduces an early F-triggering step but enhances a late fusion pore formation step in the NiV membrane fusion cascade. Thus, our results expand our mechanistic understanding of the paramyxoviral/henipaviral entry and cell-cell fusion processes.IMPORTANCE Cholesterol has been implicated in various steps of the viral life cycle for different enveloped viruses. Nipah virus (NiV) is a highly pathogenic enveloped virus in the Henipavirus genus within the Paramyxoviridae family, capable of causing a high mortality rate in humans and high morbidity in domestic and agriculturally important animals. The role of cholesterol for NiV or the henipaviruses is unknown. Here, we show that the levels of cholesterol influence the levels of NiV-induced cell-cell membrane fusion during syncytium formation and virus-cell membrane fusion during viral entry. Furthermore, the specific role of cholesterol in membrane fusion is not well defined for the paramyxoviruses. We show that the levels of cholesterol affect an early F-triggering step and a late fusion pore formation step during the membrane fusion cascade. Thus, our results expand our mechanistic understanding of the viral entry and cell-cell fusion processes, which may aid the development of antivirals.

Evidence of a Near-Threshold Resonance in

A narrow near-threshold proton-emitting resonance (E_{x}=11.4 MeV, J^{π}=1/2^{+}, and Γ_{p}=4.4 keV) was directly observed in ^{11}B via proton resonance scattering. This resonance was previously inferred in the ß-delayed proton emission of the neutron halo nucleus ^{11}Be. The good agreement between both experimental results serves as a ground to confirm the existence of such exotic decay and the particular behavior of weakly bound nuclei coupled to the continuum. R-matrix analysis shows a sizable partial decay width for both, proton and α (Γ_{α}=11 keV) emission channels.

External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications (IPPIC) Network database: individual participant data meta-analysis.

OBJECTIVE: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. METHODS: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. RESULTS: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. CONCLUSIONS: The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Light stimulation during postnatal development is not determinant for glutamatergic neurotransmission from the retinohypothalamic tract to the suprachiasmatic nucleus in rats.

The hypothalamic suprachiasmatic nucleus (SCN) is the leading circadian pacemaker in mammals, which synchronizes with environmental light through the retinohypothalamic tract (RHT). Although the SCN regulates circadian rhythms before birth, postnatal synaptic changes are needed for the RHT-SCN pathway to achieve total functional development. However, it is unknown whether visual experience affects developmental maturation. Here, we studied the effects of constant darkness (DD) rearing on the physiology (at pre- and postsynaptic levels) of glutamatergic neurotransmission between RHT and SCN during postnatal development in rats. Upon recording spontaneous and evoked excitatory postsynaptic currents (EPSCs) by electrical stimulation of RHT fibers, we found that DD animals at early postnatal ages (P3-19) exhibited different frequencies of spontaneous EPSCs and lower synaptic performance (short-term depression, release sites, and recruitment of RHT fibers) when compared with their normal light/dark (LD) counterparts. At the oldest age evaluated (P30-35), there was a synaptic response strengthening (probability of release, vesicular re-filling rate, and reduced synaptic depression) in DD rats, which functionally equaled (or surmounted) that of LD animals. Control experiments evaluating EPSCs in ventral SCN neurons of LD rats during day and night revealed no significant differences in spontaneous or evoked EPSCs by high-frequency trains in the RHT at any postnatal age. Our results suggest that DD conditions induce a compensatory mechanism in the glutamatergic signaling of the circadian system to increase the chances of synchronization to light at adult ages, and that the synaptic properties of RHT terminals during postnatal development are not critically influenced by environmental light.

Third Helical Domain of the Nipah Virus Fusion Glycoprotein Modulates both Early and Late Steps in the Membrane Fusion Cascade.

Medically important paramyxoviruses, such as measles, mumps, parainfluenza, Nipah, and Hendra viruses, infect host cells by directing fusion of the viral and cellular plasma membranes. Upon infection, paramyxoviruses cause a second type of membrane fusion, cell-cell fusion (syncytium formation), which is linked to pathogenicity. Host cell receptor binding causes conformational changes in the attachment glycoprotein (HN, H, or G) that trigger a conformational cascade in the fusion (F) glycoprotein that mediates membrane fusion. F, a class I fusion protein, contains the archetypal heptad repeat regions 1 (HR1) and 2 (HR2). It is well established that binding of HR1 and HR2 is key to fusing viral and cellular membranes. In this study, we uncovered a novel fusion-modulatory role of a third structurally conserved helical region (HR3) in F. Based on its location within the F structure, and structural differences between its prefusion and postfusion conformations, we hypothesized that the HR3 modulates triggering of the F conformational cascade (still requiring G). We used the deadly Nipah virus (NiV) as an important paramyxoviral model to perform alanine scan mutagenesis and a series of multidisciplinary structural/functional analyses that dissect the various states of the membrane fusion cascade. Remarkably, we found that specific residues within the HR3 modulate not only early F-triggering but also late extensive fusion pore expansion steps in the membrane fusion cascade. Our results characterize these novel fusion-modulatory roles of the F HR3, improving our understanding of the membrane fusion process for NiV and likely for the related Henipavirus genus and possibly Paramyxoviridae family members.IMPORTANCE The Paramyxoviridae family includes important human and animal pathogens, such as measles, mumps, and parainfluenza viruses and the deadly henipaviruses Nipah (NiV) and Hendra (HeV) viruses. Paramyxoviruses infect the respiratory tract and the central nervous system (CNS) and can be highly infectious. Most paramyxoviruses have a limited host range. However, the biosafety level 4 NiV and HeV are highly pathogenic and have a wide mammalian host range. Nipah viral infections result in acute respiratory syndrome and severe encephalitis in humans, leading to 40 to 100% mortality rates. The lack of licensed vaccines or therapeutic approaches against NiV and other important paramyxoviruses underscores the need to understand viral entry mechanisms. In this study, we uncovered a novel role of a third helical region (HR3) of the NiV fusion glycoprotein in the membrane fusion process that leads to viral entry. This discovery sets HR3 as a new candidate target for antiviral strategies for NiV and likely for related viruses.

Revision of Cerinomyces (Dacrymycetes, Basidiomycota) with notes on morphologically and historically related taxa.

Cerinomyces (Dacrymycetes, Basidiomycota) is a genus traditionally defined by corticioid basidiocarps, in contrast to the rest of the class, which is characterized by gelatinous ones. In the traditional circumscription the genus is polyphyletic, and the monotypic family Cerinomycetaceae is paraphyletic. Aiming for a more concise delimitation, we revise Cerinomyces s.l. with a novel phylogeny based on sequences of nrDNA (SSU, ITS, LSU) and protein-coding genes (RPB1, RPB2, TEF1-α). We establish that monophyletic Cerinomyces s.s. is best characterized not by the corticioid morphology, but by a combination of traits: hyphal clamps, predominantly aseptate thin-walled basidiospores, and low content of carotenoid pigments. In our updated definition, Cerinomyces s.s. encompasses five well-supported phylogenetic clades divided into two morphological groups: (i-iii) taxa with arid corticioid basidiocarps, including the generic type C. pallidus; and (iv-v) newly introduced members with gelatinous basidiocarps, like Dacrymyces enatus and D. tortus. The remaining corticioid species of Cerinomyces s.l. are morphologically distinct and belong to the Dacrymycetaceae: our analysis places the carotenoid-rich Cerinomyces canadensis close to Femsjonia, and we transfer the clamps-lacking C. grandinioides group to Dacrymyces. In addition, we address genera related to Cerinomyces s.l. historically and morphologically, such as Ceracea, Dacryonaema and Unilacryma. Overall, we describe twenty-four new species and propose nine new combinations in both Cerinomycetaceae and Dacrymycetaceae.

Nipah and Hendra Virus Glycoproteins Induce Comparable Homologous but Distinct Heterologous Fusion Phenotypes.

Nipah and Hendra viruses (NiV and HeV) exhibit high lethality in humans and are biosafety level 4 (BSL-4) paramyxoviruses in the growing genus Henipavirus The attachment (G) and fusion (F) envelope glycoproteins are both required for viral entry into cells and for cell-cell fusion, which is pathognomonic of henipaviral infections. Here, we compared the fusogenic capacities between homologous and heterologous pairs of NiV and HeV glycoproteins. Importantly, to accurately measure their fusogenic capacities, as these depend on glycoprotein cell surface expression (CSE) levels, we inserted identical extracellular tags to both fusion (FLAG tags) or both attachment (hemagglutinin [HA] tags) glycoproteins. Importantly, these tags were placed in extracellular sites where they did not affect glycoprotein expression or function. NiV and HeV glycoproteins induced comparable levels of homologous HEK293T cell-cell fusion. Surprisingly, however, while the heterologous NiV F/HeV G (NF/HG) combination yielded a hypofusogenic phenotype, the heterologous HeV F/NiV G (HF/NG) combination yielded a hyperfusogenic phenotype. Pseudotyped viral entry levels primarily corroborated the fusogenic phenotypes of the glycoprotein pairs analyzed. Furthermore, we constructed G and F chimeras that allowed us to map the overall regions in G and F that contributed to these hyperfusogenic or hypofusogenic phenotypes. Importantly, the fusogenic phenotypes of the glycoprotein combinations negatively correlated with the avidities of F-G interactions, supporting the F/G dissociation model of henipavirus-induced membrane fusion, even in the context of heterologous glycoprotein pairs.IMPORTANCE The NiV and HeV henipaviruses are BSL-4 pathogens transmitted from bats. NiV and HeV often lead to human death and animal diseases. The formation of multinucleated cells (syncytia) is a hallmark of henipaviral infections and is caused by fusion of cells coordinated by interactions of the viral attachment (G) and fusion (F) glycoproteins. We found via various assays that viral entry and syncytium formation depend on the viral origin of the glycoproteins, with HeV F and NiV G promoting higher membrane fusion levels than their counterparts. This is important knowledge, since both viruses use the same bat vector species and potential coinfections of these or subsequent hosts may alter the outcome of disease.

First Direct Measurement of

Type-I x-ray bursts can reveal the properties of an accreting neutron star system when compared with astrophysics model calculations. However, model results are sensitive to a handful of uncertain nuclear reaction rates, such as ^{22}Mg(α,p). We report the first direct measurement of ^{22}Mg(α,p), performed with the Active Target Time Projection Chamber. The corresponding astrophysical reaction rate is orders of magnitude larger than determined from a previous indirect measurement in a broad temperature range. Our new measurement suggests a less-compact neutron star in the source GS1826-24.

Effects of oral probiotic supplements on vaginal microbiota during pregnancy: a randomised, double-blind, placebo-controlled trial with microbiome analysis.

OBJECTIVE: To determine the effects on the vaginal microbiota of an oral probiotic preparation administered from early pregnancy. DESIGN: Randomised, double blind, placebo-controlled trial. SETTING: Four maternity units in the UK. POPULATION: Women aged 16 years or older recruited at 9-14 weeks' gestation. METHODS: Participants were randomly allocated to receive oral capsules of probiotic containing Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 each at 2.5 × 109 colony-forming units (CFUs) or placebo once daily from recruitment until the end of pregnancy. MAIN OUTCOME MEASURE: Rates of bacterial vaginosis (BV, defined as Nugent score ≥7) at 18-20 weeks' gestation compared by logistic regression adjusted for possible confounders. RESULTS: The primary analysis included 78% (238/304) of participants who initially consented (probiotic group 123, placebo group 115). Of these participants, 95% (227/238) reported an intake of 93% or more of the required number of capsules. The rates of BV did not differ between groups at 18-20 weeks' gestation (15% (19/123) in the probiotic group vs. 9% (10/115) in the placebo group, adjusted odds ratio 1.82, 95% confidence interval 0.64-5.19). There were also no differences between the groups in the proportion of women colonised with the probiotic strains, Escherichia coli, group B streptococci or other vaginal microbiota. There were no differences in the alpha diversity or composition of the bacterial communities between or within the probiotic and placebo groups at 9-14 and 18-20 weeks' gestation. CONCLUSIONS: Oral probiotics taken from early pregnancy did not modify the vaginal microbiota. TWEETABLE ABSTRACT: The oral probiotic preparation used in this study does not prevent BV in pregnant women.

New approach for estimating risk of miscarriage after chorionic villus sampling.

OBJECTIVE: To estimate the risk of miscarriage associated with chorionic villus sampling (CVS). METHODS: This was a retrospective cohort study of women attending for routine ultrasound examination at 11 + 0 to 13 + 6 weeks' gestation at one of eight fetal-medicine units in Spain, Belgium and Bulgaria, between July 2007 and June 2018. Two populations were included: (1) all singleton pregnancies undergoing first-trimester assessment at Hospital Clínico Universitario Virgen de la Arrixaca in Murcia, Spain, that did not have CVS (non-CVS group); and (2) all singleton pregnancies that underwent CVS following first-trimester assessment at one of the eight participating centers (CVS group). We excluded pregnancies diagnosed with genetic anomalies or major fetal defects before or after birth, those that resulted in termination and those that underwent amniocentesis later in pregnancy. We used propensity score (PS) matching analysis to estimate the association between CVS and miscarriage. We compared the risk of miscarriage of the CVS and non-CVS groups after PS matching (1:1 ratio). This procedure creates two comparable groups balancing the maternal and pregnancy characteristics that are associated with CVS, in a similar way to that in which randomization operates in a randomized clinical trial. RESULTS: The study population consisted of 22 250 pregnancies in the non-CVS group and 3613 in the CVS group. The incidence of miscarriage in the CVS group (2.1%; 77/3613) was significantly higher than that in the non-CVS group (0.9% (207/22 250); P < 0.0001). The PS algorithm matched 2122 CVS with 2122 non-CVS cases, of which 40 (1.9%) and 55 (2.6%) pregnancies in the CVS and non-CVS groups, respectively, resulted in a miscarriage (odds ratio (OR), 0.72 (95% CI, 0.48-1.10); P = 0.146). We found a significant interaction between the risk of miscarriage following CVS and the risk of aneuploidy, suggesting that the effect of CVS on the risk of miscarriage differs depending on background characteristics. Specifically, when the risk of aneuploidy is low, the risk of miscarriage after CVS increases (OR, 2.87 (95% CI, 1.13-7.30)) and when the aneuploidy risk is high, the risk of miscarriage after CVS is paradoxically reduced (OR, 0.47 (95% CI, 0.28-0.76)), presumably owing to prenatal diagnosis and termination of pregnancies with major aneuploidies that would otherwise have resulted in spontaneous miscarriage. For example, in a patient in whom the risk of aneuploidy is 1 in 1000 (0.1%), the risk of miscarriage after CVS will increase to 0.3% (0.2 percentage points higher). CONCLUSIONS: The risk of miscarriage in women undergoing CVS is about 1% higher than that in women who do not have CVS, although this excess risk is not solely attributed to the invasive procedure but, to some extent, to the demographic and pregnancy characteristics of the patients. After accounting for these risk factors and confining the analysis to low-risk pregnancies, CVS seems to increase the risk of miscarriage by about three times above the patient's background risk. Although this is a substantial increase in relative terms, in pregnancies without risk factors for miscarriage, the risk of miscarriage after CVS remains low and similar to, or slightly higher than, that in the general population. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Nuevo enfoque para estimar el riesgo de aborto después de una biopsia de vellosidades coriónicas OBJETIVO: Estimar el riesgo de aborto asociado con la biopsia de vellosidades coriónicas (BVC). MÉTODOS: Se trata de un estudio retrospectivo de cohorte de mujeres que acudieron a un examen ecográfico de rutina entre las 11+0 y las 13+6 semanas de gestación a una de entre un total de ocho centros de medicina fetal en España, Bélgica y Bulgaria, entre julio de 2007 y junio de 2018. En el estudio se incluyeron dos poblaciones: 1) todos los embarazos con feto único sometidos a evaluación del primer trimestre en el Hospital Clínico Universitario Virgen de la Arrixaca de Murcia (España), a las que no se les hizo una BVC (grupo no BVC); y 2) todos los embarazos con feto único sometidos a BVC tras la evaluación del primer trimestre en uno de los ocho centros participantes (grupo BVC). Se excluyeron los embarazos diagnosticados con anomalías genéticas o defectos fetales importantes antes o después del nacimiento, los que resultaron en una interrupción y los que más tarde se sometieron a amniocentesis durante el embarazo. Para estimar la relación entre la BVC y el aborto espontáneo se utilizó el pareamiento por puntaje de propensión (PPP). Se comparó el riesgo de aborto de los grupos BVC y no BVC después del pareamiento PPP (razón 1:1). Este procedimiento creó dos grupos comparables en los que las características de la madre y el embarazo que se asocian con la BVC estaban equilibradas, de manera similar a cómo funciona la aleatorización en un ensayo clínico aleatorizado. RESULTADOS: La población de estudio consistió en 22.250 embarazos en el grupo no BVC y 3.613 en el grupo BVC. La incidencia de abortos en el grupo BVC (2,1%; 77/3.613) fue significativamente mayor que en el grupo no BVC (0,9% (207/22.250); P<0,0001). El algoritmo del PPP emparejó 2.122 BVC con 2.122 casos no BVC, de los cuales 40 (1,9%) y 55 (2,6%) embarazos en los grupos BVC y no BVC, respectivamente, resultaron en un aborto espontáneo (razón de momios (RM), 0,72 (IC 95%, 0,48-1,10); P=0,146). Se encontró una interacción significativa entre el riesgo de aborto espontáneo después de una BVC y el riesgo de aneuploidía, lo que sugiere que el efecto de la BVC en el riesgo de aborto espontáneo difiere según las características del contexto. Concretamente, cuando el riesgo de aneuploidía es bajo, el riesgo de aborto después de una BVC aumenta (RM, 2,87 (IC 95%, 1,13-7,30)) y cuando el riesgo de aneuploidía es alto, paradójicamente el riesgo de aborto después de una BVC se reduce (RM, 0,47 (IC 95%, 0,28-0,76)), presumiblemente debido al diagnóstico prenatal y a la interrupción de embarazos con aneuploidías importantes que, de otro modo, hubieran provocado un aborto espontáneo. Por ejemplo, en una paciente para quien el riesgo de aneuploidía es de 1 entre 1000 (0,1%), el riesgo de aborto después de la BVC aumenta al 0,3% (0,2 puntos porcentuales más alto). CONCLUSIONES: El riesgo de aborto espontáneo en las mujeres que se someten a una BVC es aproximadamente un 1% mayor que el de las mujeres a las que no se les hace, aunque este exceso de riesgo no se atribuye únicamente al procedimiento agresivo sino, en cierta medida, a las características demográficas y del embarazo de cada paciente. Después de tener en cuenta estos factores de riesgo y limitar el análisis a los embarazos de bajo riesgo, la BVC parece triplicar aproximadamente el riesgo de aborto en comparación con el riesgo de fondo de la paciente. Aunque se trata de un aumento sustancial en términos relativos, en los embarazos sin factores de riesgo de aborto, después de una BVC el riesgo de aborto sigue siendo bajo y similar, o ligeramente superior, al de la población en general. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Stingray spear injury to the pediatric spinal cord: case report and review of the literature.

Stingray injuries are rare, mostly causing injuries to the lower extremities but occasionally fatal if there is direct puncture of the thorax, abdomen, or neck. Direct combined stingray injury to the central nervous system has not been reported in the literature. Herein we present the case of a 12-year-old boy who, while wading at the seashore of the Costa Rica's Pacific Ocean, sustained a combined oblique penetrating injury to the C6 vertebra caused by a Stingray. He initially presented to the hospital with a complete asymmetric right C6/left T1 ASIA A examination, priapism, and loss of anal sphincter tone. Imaging revealed fracture of the posterior elements of C6 with an oblique trajectory into the left radicular foramen. T2W images did not reveal anatomical section but rather edema and minor bleeding in the epidural space. The patient underwent medical management and serial imaging. During the next 3 months, there was recovery of sensation on the right hemi body, bilateral paresthesias and asymmetric progressive improvement in strength on both legs. Acute care management and midterm term follow up are provided, along with a review of the literature for salient management considerations when evaluating and treating combined penetrating and envenomation injuries caused by stingrays. To our knowledge, this is the first report of such injury to the spine.

Correction to: Stingray spear injury to the pediatric spinal cord: case report and review of the literature.

The original version of this article unfortunately contained an error in the spelling of the last name of one of the co-authors. The corresponding author did not notice that the last name of one of the co-authors, Nathan Shlobin, was misspelled as "Schlobin". The correct spelling of his last name is "Shlobin". Given in this article is the corrected author name.

Genotoxicity in fishes environmentally exposed to As, Se, Hg, Pb, Cr and toxaphene in the lower Colorado River basin, at Mexicali valley, Baja California, México.

The environmental exposure to As, Se, Hg, Pb, Cr and toxaphene was assessed for 11 freshwater fish species in irrigation channels, agricultural return flow drains, a drain collecting lagoon and sections of the Colorado River at the Mexicali valley in Baja California, México, during August 2015-April 2016. Arsenic (2.90 ng ml-1) and Se (1.41 ng ml-1) in water had the highest concentrations in the return flow drains (Hardy River and Xochimilco Lagoon, respectively). However, fish axial muscle tissue had the highest concentration of Se (8.3 µg g-1) and Hg (0.36 µg g-1) in Colorado River fresh water, while As (1.7 µg g-1) in Hardy River fish was highest. Selenium concentrations in all fishes and toxaphene in Cyprinus carpio and Ameiurus natalis are above the safe levels for human consumption (0.3 µg g-1 and 180 ng g-1 respectively). Toxaphene was detected in the fish axial tissue, having the highest concentrations in Poecilia latipinna (690 ng g-1) in the Colorado River. The low proportion of the 8-Cl toxaphene congeners in fish suggests degradation of this pollutant. Tilapia. sp. cf. zillii had the most genotoxic damage with 7.4 micronucleated erythrocytes per 10,000 erythrocytes in Xochimilco Lagoon and 2 in Hardy River. The genotoxicity in all the fish species studied was significantly correlated to the concentrations of As and Se in water.

Phylogeny and character evolution in the Dacrymycetes, and systematics of Unilacrymaceae and Dacryonaemataceae fam. nov.

We present a multilocus phylogeny of the class Dacrymycetes, based on data from the 18S, ITS, 28S, RPB1, RPB2, TEF-1α, 12S, and ATP6 DNA regions, with c. 90 species including the types of most currently accepted genera. A variety of methodological approaches was used to infer phylogenetic relationships among the Dacrymycetes, from a supermatrix strategy using maximum likelihood and Bayesian inference on a concatenated dataset, to coalescence-based calculations, such as quartet-based summary methods of independent single-locus trees, and Bayesian integration of single-locus trees into a species tree under the multispecies coalescent. We evaluate for the first time the taxonomic usefulness of some cytological phenotypic characters, i.e., vacuolar contents (vacuolar bodies and lipid bodies), number of nuclei of recently discharged basidiospores, and pigments, with especial emphasis on carotenoids. These characters, along with several others traditionally used for the taxonomy of this group (basidium shape, presence and morphology of clamp connections, morphology of the terminal cells of cortical/marginal hyphae, presence and degree of ramification of the hyphidia), are mapped on the resulting phylogenies and their evolution through the class Dacrymycetes discussed. Our analyses reveal five lineages that putatively represent five different families, four of which are accepted and named. Three out of these four lineages correspond to previously circumscribed and published families (Cerinomycetaceae, Dacrymycetaceae, and Unilacrymaceae), and one is proposed as the new family Dacryonaemataceae. Provisionally, only a single order, Dacrymycetales, is accepted within the class. Furthermore, the systematics of the two smallest families, Dacryonaemataceae and Unilacrymaceae, are investigated to the species level, using coalescence-based species delimitation on multilocus DNA data, and a detailed morphological study including morphometric analyses of the basidiospores. Three species are accepted in Dacryonaema, the type, Da. rufum, the newly combined Da. macnabbii (basionym Dacrymyces macnabbii), and a new species named Da. macrosporum. Two species are accepted in Unilacryma, the new U. bispora, and the type, U. unispora, the latter treated in a broad sense pending improved sampling across the Holarctic.

Constraining the Neutron Star Compactness: Extraction of the

The ^{23}Al(p,γ)^{24}Si reaction is among the most important reactions driving the energy generation in type-I x-ray bursts. However, the present reaction-rate uncertainty limits constraints on neutron star properties that can be achieved with burst model-observation comparisons. Here, we present a novel technique for constraining this important reaction by combining the GRETINA array with the neutron detector LENDA coupled to the S800 spectrograph at the National Superconducting Cyclotron Laboratory. The ^{23}Al(d,n) reaction was used to populate the astrophysically important states in ^{24}Si. This enables a measurement in complete kinematics for extracting all relevant inputs necessary to calculate the reaction rate. For the first time, a predicted close-lying doublet of a 2_{2}^{+} and (4_{1}^{+},0_{2}^{+}) state in ^{24}Si was disentangled, finally resolving conflicting results from two previous measurements. Moreover, it was possible to extract spectroscopic factors using GRETINA and LENDA simultaneously. This new technique may be used to constrain other important reaction rates for various astrophysical scenarios.