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Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Congenital ichthyosis (CI) constitutes a large etiologically and phenotypically heterogeneous group of infrequent genetic cornification disorders marked by impaired epidermal barrier function, with highly variable outcome and severity. In newborns with severe ichthyosis, the consequence of this disrupted barrier can be particularly dangerous, at times life-threatening, with increased susceptibility to respiratory failure, infection, and dramatically increased metabolic demands due to increased epidermal turnover and transepidermal water loss. We report five cases of congenital ichthyosis, admitted in the last 4 years to our NICU. This article explores different neonatal presentations of ichthyoses, describes potential complications and causes of morbidity and mortality, and discusses management considerations relevant to the neonatal period. Case 1 and 2 are siblings suffering from Harlequin ichthyosis, successfully treated with acitretin with no significant side effects. Case 3 is a case of severe CI, called Netherton syndrome, with poor prognosis. Case 4 and 5 are an example of collodion babies. All cases required NICU admission for intensive skin care and hydration, and some requested respiratory support. Case three died due to necrotizing enterocolitis and sepsis. Although congenital ichthyosis is fairly rare, it is important for the neonatologist to be aware of this heterogeneous disorder, as the perinatal period represents a particularly critical stage. Severe forms of CI require admission to a NICU and a thoughtful interdisciplinary approach to improve prognosis and to successfully treat complications. An early oral retinoid therapy should be considered in Harlequin ichthyosis. [ABSTRACT FROM AUTHOR]

Since the beginning of the COVID-19 pandemic, the impact of superinfections in intensive care units (ICUs) has progressively increased, especially carbapenem-resistant Acinetobacter baumannii (CR-Ab). This observational, multicenter, retrospective study was designed to investigate the characteristics of COVID-19 ICU patients developing CR-Ab colonization/infection during an ICU stay and evaluate mortality risk factors in a regional ICU network. A total of 913 COVID-19 patients were admitted to the participating ICUs; 19% became positive for CR-Ab, either colonization or infection (n = 176). The ICU mortality rate in CR-Ab patients was 64.7%. On average, patients developed colonization or infection within 10 ± 8.4 days from ICU admission. Scores of SAPS II and SOFA were significantly higher in the deceased patients (43.8 ± 13.5, p = 0.006 and 9.5 ± 3.6, p < 0.001, respectively). The mortality rate was significantly higher in patients with extracorporeal membrane oxygenation (12; 7%, p = 0.03), septic shock (61; 35%, p < 0.001), and in elders (66 ± 10, p < 0.001). Among the 176 patients, 129 (73%) had invasive infection with CR-Ab: 105 (60.7%) Ventilator-Associated Pneumonia (VAP), and 46 (26.6%) Bloodstream Infections (BSIs). In 22 cases (6.5%), VAP was associated with concomitant BSI. Colonization was reported in 165 patients (93.7%). Mortality was significantly higher in patients with VAP (p = 0.009). Colonized patients who did not develop invasive infections had a higher survival rate (p < 0.001). Being colonized by CR-Ab was associated with a higher risk of developing invasive infections (p < 0.001). In a multivariate analysis, risk factors significantly associated with mortality were age (OR = 1.070; 95% CI (1.028−1.115) p = 0.001) and CR-Ab colonization (OR = 5.463 IC95% 1.572−18.988, p = 0.008). Constant infection-control measures are necessary to stop the spread of A. baumannii in the hospital environment, especially at this time of the SARS-CoV-2 pandemic, with active surveillance cultures and the efficient performance of a multidisciplinary team.

Plants respond to abiotic stress stimuli, such as water deprivation, through a hierarchical cascade that includes detection and signaling to mediate transcriptional and physiological changes. The phytohormone abscisic acid (ABA) is well-characterized for its regulatory role in these processes in response to specific environmental cues. ABA-mediated changes in gene expression have been demonstrated to be temporally-dependent, however, the genome-wide timing of these responses are not well-characterized in the agronomically important crop plant Zea mays (maize). ABA-mediated responses are synergistic with other regulatory mechanisms, including the plant-specific RNA-directed DNA methylation (RdDM) epigenetic pathway. Our prior work demonstrated that after relatively long-term ABA induction (8 h), maize plants homozygous for the mop1-1 mutation, defective in a component of the RdDM pathway, exhibit enhanced transcriptional sensitivity to the phytohormone. At this time-point, many hierarchically positioned transcription factors are differentially expressed resulting in primary (direct) and secondary (indirect) transcriptional outcomes. To identify more immediate and direct MOP1-dependent responses to ABA, we conducted a transcriptomic analysis using mop1-1 mutant and wild type plants treated with ABA for 1 h. One h of ABA treatment was sufficient to induce unique categories of differentially expressed genes (DEGs) in mop1-1 . A comparative analysis between the two time-points revealed that distinct epigenetically-regulated changes in gene expression occur within the early stages of ABA induction, and that these changes are predicted to influence less immediate, indirect transcriptional responses. Homology with MOP1-dependent siRNAs and a gene regulatory network (GRN) were used to identify putative immediate and indirect targets, respectively. By manipulating two key regulatory networks in a temporal dependent manner, we identified genes and biological processes regulated by RdDM and ABA-mediated stress responses. Consistent with mis-regulation of gene expression, mop1-1 homozygous plants are compromised in their ability to recover from water deprivation. Collectively, these results indicate transcriptionally and physiologically relevant roles for MOP1-mediated regulation of gene expression of plant responses to environmental stress., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Madzima, Vendramin, Lynn, Lemert, Lu and McGinnis.)

Plants are subjected to extreme environmental conditions and must adapt rapidly. The phytohormone abscisic acid (ABA) accumulates during abiotic stress, signaling transcriptional changes that trigger physiological responses. Epigenetic modifications often facilitate transcription, particularly at genes exhibiting temporal, tissue-specific and environmentally-induced expression. In maize ( Zea mays ), MEDIATOR OF PARAMUTATION 1 (MOP1) is required for progression of an RNA-dependent epigenetic pathway that regulates transcriptional silencing of loci genomewide. MOP1 function has been previously correlated with genomic regions adjoining particular types of transposable elements and genic regions, suggesting that this regulatory pathway functions to maintain distinct transcriptional activities within genomic spaces, and that loss of MOP1 may modify the responsiveness of some loci to other regulatory pathways. As critical regulators of gene expression, MOP1 and ABA pathways each regulate specific genes. To determine whether loss of MOP1 impacts ABA-responsive gene expression in maize, mop1-1 and Mop1 homozygous seedlings were subjected to exogenous ABA and RNA-sequencing. A total of 3,242 differentially expressed genes (DEGs) were identified in four pairwise comparisons. Overall, ABA-induced changes in gene expression were enhanced in mop1-1 homozygous plants. The highest number of DEGs were identified in ABA-induced mop1-1 mutants, including many transcription factors; this suggests combinatorial regulatory scenarios including direct and indirect transcriptional responses to genetic disruption ( mop1-1 ) and/or stimulus-induction of a hierarchical, cascading network of responsive genes. Additionally, a modest increase in CHH methylation at putative MOP1-RdDM loci in response to ABA was observed in some genotypes, suggesting that epigenetic variation might influence environmentally-induced transcriptional responses in maize., (Copyright © 2020 Vendramin et al.)

A sequential TIE procedure combining in a single framework Phase I manipulations and Phase II methods, including chemical analyses and complementary Phase I treatments, was proposed for characterization and identification of toxicants of concern in estuarine environments. Interstitial water was chosen as test matrix and embryo-larval development with the bivalve Crassostrea gigas as toxicity endpoint. TIE treatments included addition of Ulva rigida and elution through zeolite column for addressing effects due to ammonia, addition of EDTA and elution through a Cation-Exchange Solid-Phase Extraction column for characterize metals, and elution through two different type of polymers (XAD and DPA) with different affinity for polar and nonpolar organic pollutants. Chemical analyses concerned determination of ammonia and trace elements in the untreated sample and after manipulation intended to remove or modify bioavailability of ammonia and metals. The "hybrid" Phase I-Phase II TIE sequence proved to be a reliable and effective tool for the identification of main toxicant of concern in a highly toxic and contaminated interstitial water sample, also in presence of high concentration of potential confounding factors (ammonia). The addition of U. rigida was the more reliable treatment for the removal of ammonia, due to the concurrent release of particles and potentially toxic elements, such as Ba, Rb, and Tl by zeolite column, which may increase toxicity in the post-column sample. The combined use of polymers with different affinity for the various classes of organic pollutants was essential to identify the contribution of polar organic compounds to the observed toxicity.

With the emergence of massively parallel sequencing, genomewide expression data production has reached an unprecedented level. This abundance of data has greatly facilitated maize research, but may not be amenable to traditional analysis techniques that were optimized for other data types. Using publicly available data, a gene coexpression network (GCN) can be constructed and used for gene function prediction, candidate gene selection, and improving understanding of regulatory pathways. Several GCN studies have been done in maize ( Zea mays ), mostly using microarray datasets. To build an optimal GCN from plant materials RNA-Seq data, parameters for expression data normalization and network inference were evaluated. A comprehensive evaluation of these two parameters and a ranked aggregation strategy on network performance, using libraries from 1266 maize samples, were conducted. Three normalization methods and 10 inference methods, including six correlation and four mutual information methods, were tested. The three normalization methods had very similar performance. For network inference, correlation methods performed better than mutual information methods at some genes. Increasing sample size also had a positive effect on GCN. Aggregating single networks together resulted in improved performance compared to single networks., (© 2017 American Society of Plant Biologists. All Rights Reserved.)

Epigenetic gene regulation is important for proper development and gene expression in eukaryotes. Maize has a large and complex genome that includes abundant repetitive sequences which are frequently silenced by epigenetic mechanisms, making it an ideal organism to study epigenetic gene regulation. Epigenetic modifications are chromosome-bound, heritable changes to the genome that do not affect the DNA sequence, and can include DNA methylation, histone modification, and RNA processing. Our appreciation and understanding of epigenetic regulation has grown with the field since its inception ∼65 years ago. Early examples of epigenetic regulation were often associated with transposable elements, starting with McClintock's early work in the 1950s. The observation of other intriguing phenotypes segregating in non-Mendelian ratios in the 1950s provided material for genetic screens that allowed for mechanistic studies of epigenetic regulation that have come to fruition within the past 20 years. The relationship between epigenetic mechanisms and genome organization has become clear with the application of new technologies to characterize maize epigenomes. Our understanding of epigenetic control of gene expression now encompasses the context of genes relative to DNA methylation, chromatin structure, and transposable element content., (Copyright © 2017 Elsevier Inc. All rights reserved.)