Prospective Randomized Observational Pilot Trial Evaluating the Effect of Information of Early Childhood Intervention on Stress Levels of Parents of Extremely Low Gestational Age Infants at the NICU.

It is not known to what extent early information on early childhood intervention (ECI) by ECI professionals reduces or increases stress levels of parents having an extremely preterm infant at the neonatal intensive care unit (NICU). Using an observational pilot study, we gave information on ECI in a randomized matter to parents of an extremely low gestational age newborn (ELGAN) at the chronological age of 3-4 weeks (cases) or not (controls). After informed consent, parents judged the infants at the age of 5-7 weeks with the Parental Stressor Scales: Neonatal Intensive Care Unit [PSS: NICU test has three subscales = "Sights and Sounds" (five items), "Parental Role Alteration" (14 items), and "Look and Behave" (seven items)]. Total scales score and subscales scores were comparable between 13 cases and 13 controls over a study period of 1.5 years. Total scores were 9.32 ± 0.72 in the cases compared to 10.02 ± 0.76 in the controls, (95% CI -6.93 to 4.93). Overall, the cases scored lower in most of the items. Early information on ECI at the NICU was provided to parents with an ELGAN did not result in higher stress levels measured with the PSS: NICU. Whether early information on ECI is a strategy, which might be able to reduce parental stress levels, has to be proven in larger studies.

Prospective Randomized Observational Pilot Trial Evaluating the Effect of Different Durations of Interdisciplinary Early Intervention and Family Support in Parents of Very Low Birth Weight Infants (Early Bird Study).

Background: Early childhood intervention (ECI) is a holistic approach for infants with or at risk for psychomotor and/or cognitive and/or behavioral impairment. It aims to optimally support them and positively influence their neurodevelopmental outcome. The right dosage of intervention and when the intervention should start are still to be determined. Hypothesis: Parents are more satisfied when the duration of ECI is longer (120 min once a week) than the usual 90-min session. Methods: We developed a parental questionnaire (both mother and father) that evaluated the level of satisfaction of parents with the intervention. We compared 120 with 90 min of ECI per week during the school year 2017/18. Included were parents of very low birth weight infants (<1,500 g) following informed consent. ECI was initiated at the NICU at an infant age of ≥ 2 weeks. Parents were randomized (https://www.randomizer.at/) to a 120- or 90-min duration and had to answer the questionnaire to the approximate time-point of 1, 3, and 6 months. Answers were classified as strongly agree, agree, neither agree nor disagree, disagree, and strongly disagree except for the last question, which directly rated the ECI professional. Results: Eleven fathers (55%) and 19 mothers (95%) of the 10 parents of each group participated in the study. Demographic data did not differ between groups, and the median time-points of questionnaire answers were 77, 137, and 220 days, respectively. Overall, 120-min ECI sessions were not superior to 90-min sessions for both parents regarding parental satisfaction during the study time. We found no differences between fathers and mothers and minimal changes over time. All parents were satisfied with the ECI professionals, irrespective of ECI duration. Conclusion: An ECI duration of 120 min once per week was not superior to a 9- min duration regarding parental satisfaction with ECI professionals and their work.

Defective removal of ribonucleotides from DNA promotes systemic autoimmunity.

Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2-associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage-associated pathways in the initiation of autoimmunity.

Single-stranded nucleic acids promote SAMHD1 complex formation.

SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy that mimics congenital viral infection and that phenotypically overlaps with the autoimmune disease systemic lupus erythematosus. Both disorders are characterized by activation of the antiviral cytokine interferon-α initiated by immune recognition of self nucleic acids. Here we provide first direct evidence that SAMHD1 associates with endogenous nucleic acids in situ. Using fluorescence cross-correlation spectroscopy, we demonstrate that SAMHD1 specifically interacts with ssRNA and ssDNA and establish that nucleic acid-binding and formation of SAMHD1 complexes are mutually dependent. Interaction with nucleic acids and complex formation do not require the SAM domain, but are dependent on the HD domain and the C-terminal region of SAMHD1. We finally demonstrate that mutations associated with AGS exhibit both impaired nucleic acid-binding and complex formation implicating that interaction with nucleic acids is an integral aspect of SAMHD1 function.