Surface scattering characteristics and the measurement of particulate contamination

Surface scattering measurement techniques can be adopted for use in spacecraft contamination control programs. A witness mirror measurement program was developed and implemented for the NASA Cosmic Background Explorer (COBE) spacecraft. Scattering measurements were obtained before and after a qualification level vibration test for several COBE prototype instruments. The measurements indicate that a significant amount of particle redistribution occurred during the vibration test. The methodology used and the results obtained from this monitoring program are discussed

New insights into the basis of neurogenesis defects in Kabuki syndrome

Chromatin modifiers act to coordinate gene expression critical to neuronal differentiation from neural stem/progenitor cells (NSPCs). Loss-of-function variants in genes encoding two such enzymes, lysine-specific methyltransferase 2D (KMT2D) and lysine-specific demethylase 6A (KDM6A/UTX) cause the congenital, multisystem intellectual disability (ID) disorder Kabuki syndrome (KS1 and KS2, respectively). A mouse model of KS1, Kmt2d(+/βgeo), demonstrated visuospatial memory impairments and decreased adult hippocampal neurogenesis in the dentate gyrus (DG). These were reversible upon post-natal treatment by histone deacetylase inhibition (HDACi), but underlying cellular and molecular mechanisms are poorly understood. Here, we moved forward with 3 hypotheses: (1) a dietary alternative may provide a more tolerable therapeutic avenue for chromatin opening in KS, (2) gene expression studies in KMT2D-deficient neuronal cells would yield novel insights into the pathogenesis of KS, and (3) comparison of phenotypes and gene expression abnormalities in KS1 and KS2 could yield a deeper understanding of the molecular mechanisms causing KS-associated ID. We describe the generation and characterization of multiple novel models of KS1 in human and mouse systems. Specifically, I report cell-autonomous defects in proliferation, cell cycle, and survival, accompanied by precocious NSPC maturation in several KMT2D-deficient model systems. Transcriptional suppression in KMT2D-deficient cells produced strong perturbation of hypoxia-responsive metabolism pathways. Functional experiments confirmed abnormalities of cellular hypoxia responses in KMT2D-deficient neural cells, and accelerated NSPC maturation in vivo. These findings support a model in which loss of KMT2D function suppresses expression of oxygen-responsive gene programs that are important to neural progenitor maintenance; this causes precocious neuronal differentiation in a mouse model of KS1. Then characterizing a KS2 mouse model, Kdm6a(tm1d), I found defects of adult hippocampal neurogenesis, cell cycle, and other phenotypes, that suggest shared etiologic mechanisms in KS2 and KS1. This work is the first to identify the specific cellular and molecular defects that occur with loss-of-function of KMT2D and KDM6A in neural model systems. Furthermore, we identify cellular energy metabolism pathways as a critical molecular target in KS-related gene expression alterations, providing novel insights that could inform the treatment of KS

Preterm birth is not associated with asymptomatic/mild SARS-CoV-2 infection per se: Pre-pregnancy state is what matters

Evidence for the real impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on preterm birth is unclear, as available series report composite pregnancy outcomes and/or do not stratify patients according to disease severity. The purpose of the research was to determine the real impact of asymptomatic/mild SARS-CoV-2 infection on preterm birth not due to maternal respiratory failure. This case-control study involved women admitted to Sant Anna Hospital, Turin, for delivery between 20 September 2020 and 9 January 2021. The cumulative incidence of Coronavirus disease-19 was compared between preterm birth (case group, n = 102) and full-term delivery (control group, n = 127). Only women with spontaneous or medically-indicated preterm birth because of placental vascular malperfusion (pregnancy-related hypertension and its complications) were included. Current or past SARS-CoV-2 infection was determined by nasopharyngeal swab testing and detection of IgM/IgG antibodies in blood samples. A significant difference in the cumulative incidence of Coronavirus disease-19 between the case (21/102, 20.5%) and the control group (32/127, 25.1%) (P= 0.50) was not observed, although the case group was burdened by a higher prevalence of three known risk factors (body mass index > 24.9, asthma, chronic hypertension) for severe Coronavirus disease-19. Logistic regression analysis showed that asymptomatic/mild SARS-CoV-2 infection was not an independent predictor of spontaneous and medically-indicated preterm birth due to pregnancy-related hypertension and its complications (0.77; 95% confidence interval, 0.41-1.43). Pregnant patients without comorbidities need to be reassured that asymptomatic/mild SARS-CoV-2 infection does not increase the risk of preterm delivery. Preterm birth and severe Coronavirus disease-19 share common risk factors (i.e., body mass index > 24.9, asthma, chronic hypertension), which may explain the high rate of indicated preterm birth due to maternal conditions reported in the literature

Probabilistic cost-effectiveness analysis of controlled ovarian stimulation with recombinant FSH plus recombinant LH vs. human menopausal gonadotropin for women undergoing IVF

Background The association of recombinant FSH plus recombinant LH in 2:1 ratio may be used not only to induce ovulation in anovulatory women with hypogonadotropic hypogonadism but also to achieve multiple follicular developments in human IVF. The aim of this analysis was to estimate the cost-effectiveness of Controlled Ovarian Stimulation (COS) with recombinant FSH (rFSH) plus recombinant LH (rLH) in comparison with highly purified human menopausal gonadotropin (HP-hMG) in the woman undergoing in vitro fertilization (IVF) in Italy. Methods A probabilistic decision tree was developed to simulate patients undergoing IVF, either using r-FSH + r-LH or HP-hMG to obtain COS. The model considers the National Health System (NHS) perspective and a time horizon equal to two years. Simulations were reported considering the number of retrieved oocytes (5–9, 10–15 and > 15) and transition probabilities were estimated through specific analyses carried out on the population of 848 women enrolled in the real-life. Results The model estimated that patients undertaking therapeutic protocol with r-FSH + r-LH increase the general success rate (+ 6.6% for pregnancy). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) of r-FSH + r-LH was below the willingness to pay set at €20,000 for all the considered scenarios. Conclusions The cost-utility analysis demonstrated that the r-FSH + r-LH is a cost-effective option for the Italian National Health System (NHS)