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Dextro-transposition of the great arteries (D-TGA) is a critical congenital heart defect that can impact neurodevelopment due to cerebral perfusion and oxygenation disorders followed by alterations in synaptogenesis, gyrification, sulcation, and the microstructure. Brain injuries can occur both pre-operatively and postoperatively, especially white matter injuries, neuronal loss, and stroke. Materials and Methods : In a retrospective study conducted at a tertiary center between 2016 and 2023, we investigated the early effects of Prostaglandin E1 (PGE1) administration and balloon atrial septostomy (BAS) on cerebral blood flow and oxygenation in inborn neonates with D-TGA. Cerebral Doppler Ultrasound in the anterior cerebral artery (ACA) was performed to assess the resistive index (RI), Peak Systolic Velocity (PSV), and End-Diastolic Velocity (EVD) before PGE1, before the BAS procedure, and 24 h after birth. Cerebral regional saturations of oxygen (crSO 2 ) and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated. D-TGA patients were divided into the PGE1 group and the PGE1 + BAS group. Age-matched healthy controls were used for comparison. Results : All 83 D-TGA newborns received PGE1 within two hours after delivery, of whom 46 (55.42%) underwent BAS. In addition, 77 newborns composed the control group. PGE1 administration increased crSO 2 from 47% to 50% in the PGE1 group, but lower than in controls at 24 h of life, while cFTOE remained elevated. The RI increased 24 h after delivery (0.718 vs. 0.769; p = 0.000002) due to decreased EDV (10.71 vs. 8.74; p < 0.0001) following PGE1 treatment. The BAS procedure resulted in a significant increase in crSO 2 from 42% to 51% at 24 h of life in the PGE1 + BAS group. Doppler parameters exhibited a similar trend as observed in the PGE1 group. Conclusions : PGE1 treatment and BAS are lifesaving interventions that may improve cerebral perfusion and oxygenation in newborns with D-TGA during the transition period, as reflected by increasing SpO 2 and crSO 2 .

Background and Objectives: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤ 32 weeks of gestational age (GA) within 24 h of birth., Materials and Methods: It is a prospective study conducted from 1 March 2022 to 31 December 2023 in a tertiary academic center. In-born infants ≤ 32 weeks of gestation (n = 88) were enrolled. The study group was further divided into surfactant (n = 44) and non-surfactant (n = 44) subgroups., Results: A total of 76% of the preterm infants who received surfactant therapy (RRR = 0.839) recorded an increase in Kindler score at 24 h of life (1 - RR = 1 - 0.24 = 76%). Surfactant administration was significantly associated with decreased pre-ductal diastolic pressure (29.9 mmHg vs. 34.8 mmHg, p = 0.0231), post-ductal diastolic pressure (28.7 mmHg vs. 32.2 mmHg, p = 0.0178), pre-ductal MAP (41.6 mmHg vs. 46.5 mmHg, p = 0.0210), and post-ductal MAP (41.0 mmHg vs. 45.3 mmHg, p = 0.0336). There were no significant changes in ductus arteriosus parameters at 24 h of life., Conclusions: Early surfactant administration does not affect the status of ductus arteriosus in preterm infants ≤ 32 weeks of gestational age at 24 h of life.

Background and Objectives : The purpose of this study to investigate if the early variations in the hematological profile could be a useful tool in the prediction and evaluation of intraventricular hemorrhage. Materials and Methods : It is a retrospective study conducted between 1 January 2017 and 31 December 2022, in a tertiary academic center. In-born infants ≤ 28 weeks of gestation ( n = 134) were enrolled. The study group of infants with all grades of IVH was further divided into mild IVH subgroups (grades 1 and 2) and severe IVH subgroups (grades 3 and 4); the control group included infants without IVH. Results : The prevalence of IVH was 35.8% ( n = 48 of 134 infants-study group). We identified significantly lower median values of HGB ( p = 0.0312) and HCT ( p = 0.0172) in all grades of the IVH group at birth as compared with control, followed by a significantly higher drop in MCV ( p = 0.0146) and MCH ( p = 0.0002) in the fourth day of life. Conclusions : Extremely preterm infants with IVH may have lower HTC and HGB values at birth, together with a decrease in MCH and MCHC and increase in MPV. The predictive model based on logistic regression analysis could predict the probability of the occurrence of IVH according to their values.

Background: Adequate perinatal management is essential in caring for extremely preterm (EP) infants. We aimed to evaluate and compare the impact of different protocols on short-term outcomes., Methods: A retrospective study was conducted on EP infants in a Romanian perinatal tertiary center during 2008-2012 and 2018-2022., Results: Data on 270 EP infants (121 in period I, 149 in period II) were analyzed collectively and stratified into two subgroups by gestational age. Initial FiO 2 administration (100% vs. 40%% p < 0.001), lung recruitment at birth (19.0% vs. 55.7% p < 0.001), early rescue surfactant administration (34.7% vs. 65.8%; p < 0.001), and the mechanical ventilation rate (98.3% vs. 58.4%; p < 0.001) were significantly improved during period II. Survival rates of EP infants significantly improved from 41.3% to 72.5%, particularly in the 26-28 weeks subgroup (63.8% to 83%). Compared to period I, the overall frequency of severe IVH decreased in period II from 30.6% to 14.1%; also, BPD rates were lower (36.6% vs. 23.4%; p = 0.045) in the 26-28 weeks subgroup. Despite improvements, there were no significant differences in the frequencies of NEC, sepsis, PVL, ROP, or PDA., Conclusions: Implementing evidence-based clinical guidelines can improve short-term outcomes.

Introduction: This study is part of a European survey on delivery room practices endorsed by the Union of European Neonatal and Perinatal Societies (UENPS) and the Romanian Association of Neonatology (ANR). The aim of our study was to evaluate the current neonatal resuscitation practices in Romanian maternity hospitals and to compare the results between level III and level II centers., Material and Methods: The questionnaire was distributed through ANR by email link to heads of neonatal departments of 53 Romanian maternity hospitals with more than one thousand of births per year between October 2019 and September 2020, having 2018 as the reference year for data collection., Results: The overall response rate to the questionnaire was 62.26% (33/53), 83.33% (15/18) for level-III centers and 51.43% (18/35) for level-II centers. Of the responding centers, 18 (54,54%) were academic hospitals, 15 (83,33%) were level III and 3 (16,67%) level II hospitals. In 2018, responding centers reported 81.139 births representing 42.66% of all Romanian births (190.170). There were significant differences between level-III and level-II maternity hospitals regarding the number of births in 2018 (3028.73±1258.38 vs 1983.78±769.99; P=0.006), lowest GA of routinely assisted infants in delivery room (25.07±3.03 weeks vs 30.44±3.28, P<0.001), inborn infants with BW<1500 admitted to neonatal intensive care unit (NICU) in 2018 (66.86±39.14 g vs 22.87±31.50 g; P=0.002), and antenatal counseling of parents before the delivery of a very preterm infant or an infant with expected problems (60% vs 22.2%; P=0.027). There were no significant differences of thermal and umbilical cord management, positive pressure delivery, heart rate assessment between responding centers., Conclusion: The adherence to new guidelines was high among responding centers regarding thermal and umbilical cord management, initial FiO 2 , but aspects like antenatal counseling, EKG monitoring, laryngeal mask, and heated/humidified gases availability and administration, and simulation-based training require further implementation., Competing Interests: Conflict of interest None to declare., (© 2024 Manuela Cucerea et al., published by Sciendo.)

Background: It is currently considered that early initiation of nasal continuous positive airway pressure, using a less invasive exogenous surfactant administration and avoiding mechanical ventilation as much as possible to minimize lung damage, may reduce mortality and/or the risk of morbidities in preterm infants. The aim of our study was to quantify our experience and compare different strategies of surfactant administration, to investigate which method is associated with less morbidity., Materials and Methods: A total of 135 preterm infants with early rescue surfactant administration for respiratory distress syndrome were included in the study. The infants were treated in an academic, Level III Neonatal Intensive Care Unit over a 3-year period between 1 December 2018 and 1 December 2021. Patients were separated into three groups: those with standard surfactant administration; those with Less Invasive Surfactant Administration-LISA; and those with Intubation Surfactant Administration Extubation-INSURE. As a primary outcome, we followed the need for intubation and mechanical ventilation within 72 h, while the secondary outcomes were major neonatal morbidities and death before discharge., Results: The surfactant administration method was significantly associated with the need for mechanical ventilation within 72 h after the procedure ( p < 0.001). LISA group infants needed less MV (OR = 0.538, p = 0.019) than INSURE group infants. We found less morbidities (OR = 0.492, p = 0.015) and deaths before discharge (OR = 0.640, p = 0.035) in the LISA group compared with the INSURE group. The analysis of morbidities found in infants who were given the surfactant by the LISA method compared with the INSURE method showed lower incidence of pneumothorax (3.9% vs. 8.8%), intraventricular hemorrhage (17.3% vs. 23.5%), intraventricular hemorrhage grade 3 and 4 (3.9% vs. 5.9%), sepsis/probable sepsis (11.5% vs. 17.7%) retinopathy of prematurity (16.7% vs. 26.7%) and deaths (3.9% vs. 5.9%). There were no significant differences between groups in frequencies of bronchopulmonary dysplasia, necrotizing enterocolitis and patent ductus arteriosus., Conclusions: Less invasive surfactant administration methods seem to have advantages regarding early need for mechanical ventilation, decreasing morbidities and death rate. In our opinion, the LISA procedure may be a good choice in spontaneously breathing infants regardless of gestational age.

Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc&#95;exon1a , a tissue-specific paternally expressed imprinted gene. Ddc&#95;exon1a shares an imprinting control region (ICR) with the imprinted, maternally expressed (outside of the central nervous system) Grb10 gene on mouse chromosome 11, but little else is known about the tissue-specific imprinted expression of Ddc&#95;exon1a . Fluorescent immunostaining localizes DDC to the developing myocardium in the pre-natal mouse heart, in a region susceptible to abnormal development and implicated in congenital heart defects in human. Ddc&#95;exon1a and Grb10 are not co-expressed in heart nor in brain where Grb10 is also paternally expressed, despite sharing an ICR, indicating they are mechanistically linked by their shared ICR but not by Grb10 gene expression. Evidence from a Ddc&#95;exon1a gene knockout mouse model suggests that it mediates the growth of the developing myocardium and a thinning of the myocardium is observed in a small number of mutant mice examined, with changes in gene expression detected by microarray analysis. Comparative studies in the human developing heart reveal a paternal expression bias with polymorphic imprinting patterns between individual human hearts at DDC&#95;EXON1a , a finding consistent with other imprinted genes in human., 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 Prickett, Montibus, Barkas, Amante, Franco, Cowley, Puszyk, Shannon, Irving, Madon-Simon, Ward, Schulz, Baldwin and Oakey.)

Microplastics (MP) are ubiquitous within the environment, but the approaches to analysis of this contaminant are currently quite diverse, with a number of analytical methods available. The comparability of results is hindered as even for a single analytical method such as Fourier transform infrared spectroscopy (FT-IR) the different instruments currently available do not allow a harmonized analysis. To overcome this limitation, a new free of charge software tool, allowing the systematic identification of MP in the environment (siMPle) was developed. This software tool allows a rapid and harmonized analysis of MP across FT-IR systems from different manufacturers (Bruker Hyperion 3000, Agilent Cary 620/670, PerkinElmer Spotlight 400, and Thermo Fischer Scientific Nicolet iN10). Using the same database and the automated analysis pipeline in siMPle, MP were identified in samples that were analyzed with instruments with different detector systems as well as optical resolutions and the results discussed.

We assess how different micropollutants and microplastics, connected to wastewater are introduced into the Baltic Sea. The relevance of untreated wastewater, treated wastewater, treated and untreated rain runoff, as well as combined sewer overflow (CSO), is assessed in respect to mass balance, as well as relative inflows of micropollutants and -plastics into the Baltic Sea. To achieve this, modelling based on data on exemplary sewer systems and measured micropollutant concentrations in the single sources were used. Most compounds reach the receiving Baltic Sea via treated wastewater. A few exceptions are compounds that are removed to a very high extent in wastewater treatment plants. For these compounds, the emissions with stormwater (e.g., terbutryn) or untreated wastewater (e.g., triclosan) are dominating. Additionally, compounds that are discharged with the water that is running off urban surfaces are introduced into marine areas via rain runoff. These data are used to forecast a total mass load and concentrations that can be expected in the Baltic Sea. Massloads are expected to be between 0.1 and 5.9 t/a for triclosan and TCPP (tris (2-chloropropyl) phosphate) and 0.2 t/a for microplastic particles. The expected concentrations in open Baltic Sea waters range from 0.01 to 26 ng/L., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

p23 is a small acidic protein with intrinsic molecular chaperone activity. It is best known as a co-chaperone of the major cytosolic molecular chaperone Hsp90. p23 binds the N-terminus of Hsp90 and stabilizes the ATP-bound and N-terminally closed Hsp90 dimer. It is in this configuration that many Hsp90 clients are most stably bound. Considering the important role of p23 in the Hsp90 cycle, it came as a surprise that it is not absolutely essential for viability in the budding yeast or for mouse development. Mice without p23 develop quite normally until birth and then all die perinatally because of immature lungs. The only other apparent phenotype of late stage embryos and newborns is a skin defect, which we have further characterized here. We found that skin differentiation is impaired, and that both apoptosis and cell proliferation are augmented in the absence of p23; the consequences are a severe thinning of the stratum corneum and reduced numbers of hair follicles. The altered differentiation, spontaneous apoptosis and proliferation are all mimicked by isolated primary keratinocytes indicating that they do require p23 functions in a cell-autonomous fashion. Since the phenotype of p23-null embryos is strikingly similar to that of embryos lacking the glucocorticoid receptor, a paradigmatic Hsp90-p23 client protein, we investigated glucocorticoid signaling. We discovered that it is impaired in vivo and for some aspects in isolated keratinocytes. Our results suggest that part of the phenotype of p23-null embryos can be explained by an impact on this particular Hsp90 client, but do not exclude that p23 by itself or in association with Hsp90 affects skin development and homeostasis through yet other pathways.

The Hsp90 family of molecular chaperones includes the cytosolic isoforms Hsp90α and Hsp90β, and the mitochondrial isoform Trap1. Hsp90α/β support a large number of client proteins in the cytoplasm and the nucleus whereas Trap1 regulates oxidative phosphorylation in mitochondria. Many of the associated proteins and cellular processes are relevant to cancer, and there is ample pharmacological and genetic evidence to support the idea that Hsp90α/β and Trap1 are required for tumorigenesis. However, a direct and comparative genetic test in a mouse cancer model has not been done. Here we report the effects of deleting the Hsp90α or Trap1 genes in a mouse model of breast cancer. Neither Hsp90α nor Trap1 are absolutely required for mammary tumor initiation, growth and metastasis induced by the polyoma middle T-antigen as oncogene. However, they do modulate growth and lung metastasis in vivo and cell proliferation, migration and invasion of isolated primary carcinoma cells in vitro. Without Hsp90α, tumor burden and metastasis are reduced, correlating with impaired proliferation, migration and invasion of cells in culture. Without Trap1, the appearance of tumors is initially delayed, and isolated cells are affected similarly to those without Hsp90α. Analysis of expression data of human breast cancers supports the conclusion that this is a valid mouse model highlighting the importance of these molecular chaperones.

Introduction: Congenital heart diseases (CHD) have been reported to be responsible for 30 to 50% of infant mortality caused by congenital disabilities. In critical cases, survival of newborns with CHD depends on the patency of the ductus arteriosus (PDA), for maintaining the systemic or pulmonary circulation. The aim of the study was to assess the efficacy and side effects of PGE (prostaglandin E) administration in newborns with critical congenital heart disease requiring maintenance of the ductus arteriosus., Material and Method: All clinical and paraclinical data of 66 infants admitted to one referral tertiary level academic center and treated with Alprostadil were analyzed. Patients were divided into three groups: Group 1: PDA dependent pulmonary circulation (n=11) Group 2: PDA dependent systemic circulation (n=31) Group 3: PDA depending mixed circulation (n=24)., Results: The mean age of starting PGE1 treatment was 2.06 days, 1.91 (+/-1.44) days for PDA depending pulmonary flow, 2.39 (+/-1.62) days for PDA depending systemic flow and 1.71 (+/1.12) for PDA depending mixing circulation. PEG1 initiation was commenced 48 hours after admission for 72%, between 48-72 hours for 6%, and after 72 to 120 hours for 21% of newborns detected with PDA dependent circulation. Before PEG1 initiation the mean initial SpO2 was 77.89 (+/- 9.2)% and mean initial oxygen pressure (PaO2) was 26.96(+/-6.45) mmHg. At the point when stable wide open PDA was achieved their mean SpO2increased to 89.73 (+/-8.4)%, and PaO2 rose to 49 (+/-7.2) mmHg. During PGE1 treatment, eleven infants (16.7%) had apnea attacks, five children (7.5%) had convulsions, 33 (50%) had fever, 47 (71.2%) had leukocytosis, 52 (78.8%) had edema, 25.8% had gastrointestinal intolerance, 45.5% had hypokalemia, and 63.6% had irritability., Conclusions: For those infants with severe cyanosis or shock caused by PDA dependent heart lesions, the initiation and maintenance of PGE1 infusion is imperative. The side effects of this beneficial therapy were transient and treatable., Competing Interests: Conflicts of interest: The authors have nothing to disclose.

Southern Iberian freshwater ecosystems located at the border between the European and African plates represent a tectonically complex region spanning several geological ages, from the uplifting of the Betic Mountains in the Serravalian-Tortonian periods to the present. This area has also been subjected to the influence of changing climate conditions since the Middle-Upper Pliocene when seasonal weather patterns were established. Consequently, the ichthyofauna of southern Iberia is an interesting model system for analyzing the influence of Cenozoic tectonic and climatic events on its evolutionary history. The cyprinids Squalius malacitanus and Squalius pyrenaicus are allopatrically distributed in southern Iberia and their evolutionary history may have been defined by Cenozoic tectonic and climatic events. We analyzed MT-CYB (510 specimens) and RAG1 (140 specimens) genes of both species to reconstruct phylogenetic relationships and to estimate divergence times and ancestral distribution ranges of the species and their populations. We also assessed their levels of genetic structure and diversity as well as the amount of gene flow between populations. To investigate recent paleogeographical and climatic factors in southern Iberia, we modeled changes-through-time in sea level from the LGM to the present. Phylogenetic, geographic and population structure analyses revealed two well-supported species (S. malacitanus and S. pyrenaicus) in southern Iberia and two subclades (Atlantic and Mediterranean) within S. malacitanus. The origin of S. malacitanus and the separation of its Atlantic and Mediterranean populations occurred during the Serravalian-Tortonian and Miocene-Pliocene periods, respectively. These divergence events occurred in the Middle Pliocene and Pleistocene in S. pyrenaicus. In both species, Atlantic basins possessed populations with higher genetic diversity than Mediterranean, which may be explained by the Janda Lagoon. The isolation of S. malacitanus was earlier and related to the rising of the Betic Mountains. Divergence of its Atlantic and Mediterranean populations was associated with the creation of the freshwater systems of southern Iberia close to the Gibraltar Strait. The presence of S. pyrenaicus in southern Iberia may be the result of recent colonization associated with river capture, as demonstrated our biogeographic reconstruction., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Despite being a fundamental biological problem the control of body size and proportions during development remains poorly understood, although it is accepted that the insulin-like growth factor (IGF) pathway has a central role in growth regulation, probably in all animals. The involvement of imprinted genes has also attracted much attention, not least because two of the earliest discovered were shown to be oppositely imprinted and antagonistic in their regulation of growth. The Igf2 gene encodes a paternally expressed ligand that promotes growth, while maternally expressed Igf2r encodes a cell surface receptor that restricts growth by sequestering Igf2 and targeting it for lysosomal degradation. There are now over 150 imprinted genes known in mammals, but no other clear examples of antagonistic gene pairs have been identified. The delta-like 1 gene (Dlk1) encodes a putative ligand that promotes fetal growth and in adults restricts adipose deposition. Conversely, Grb10 encodes an intracellular signalling adaptor protein that, when expressed from the maternal allele, acts to restrict fetal growth and is permissive for adipose deposition in adulthood., Results: Here, using knockout mice, we present genetic and physiological evidence that these two factors exert their opposite effects on growth and physiology through a common signalling pathway. The major effects are on body size (particularly growth during early life), lean:adipose proportions, glucose regulated metabolism and lipid storage in the liver. A biochemical pathway linking the two cell signalling factors remains to be defined., Conclusions: We propose that Dlk1 and Grb10 define a mammalian growth axis that is separate from the IGF pathway, yet also features an antagonistic imprinted gene pair.

Developmental programming links growth in early life with health status in adulthood. Although environmental factors such as maternal diet can influence the growth and adult health status of offspring, the genetic influences on this process are poorly understood. Using the mouse as a model, we identify the imprinted gene Grb10 as a mediator of nutrient supply and demand in the postnatal period. The combined actions of Grb10 expressed in the mother, controlling supply, and Grb10 expressed in the offspring, controlling demand, jointly regulate offspring growth. Furthermore, Grb10 determines the proportions of lean and fat tissue during development, thereby influencing energy homeostasis in the adult. Most strikingly, we show that the development of normal lean/fat proportions depends on the combined effects of Grb10 expressed in the mother, which has the greater effect on offspring adiposity, and Grb10 expressed in the offspring, which influences lean mass. These distinct functions of Grb10 in mother and pup act complementarily, which is consistent with a coadaptation model of imprinting evolution, a model predicted but for which there is limited experimental evidence. In addition, our findings identify Grb10 as a key genetic component of developmental programming, and highlight the need for a better understanding of mother-offspring interactions at the genetic level in predicting adult disease risk., Competing Interests: The authors have declared that no competing interests exist.

Unlabelled: Although the absolute number of congenital structural heart disease has not changed over the years, more and more infants undergo surgical interventions in the neonatal period, increasing the number of children and adults with post surgical status of cardiac disorders. Prostaglandin E1 (PGE1) is the first line drug to maintain or reopen the ductus arteriosus, until surgical intervention can be made. Cerebral blood flow (CBF) is regulated by multiple factors, like pO2, pCO2, pH, cardiac output and systemic blood pressure. The aim of the study was to determine how CBF changes after PGE1 administration in these newborns., Materials and Methods: We studied the pO2, pCO2, mean systemic blood pressure, and cerebral blood flow velocities by colored and pulsed Doppler ultrasonography in 36 newborns with ductal dependent cardiac malformation before and after prostaglandin E1 administration, and correlated them to normal values for the age., Results: We found that cerebral blood flow velocities followed the variations of blood pressure in restricted pulmonary circulation; improvement of oxygenation went parallel with decrease of cerebral diastolic velocities, and in aortic coarctation cerebral velocities decreased after introduction of PGE1., Conclusions: PGE1 administration improved cerebral blood flow velocities in all forms of cardiac malformations, due to reorganization of cardiac output and changes in oxemia. Key

Objective: To describe three-dimensional ultrasonographic features of an ectopic pregnancy in a cesarean scar., Design: Description of a case., Setting: Case report of one patient., Patient(s): A 38-year-old women with three previous cesarean deliveries., Intervention(s): Three-dimensional ultrasonography was performed for diagnosis and treatment., Main Outcome Measure(s): Local administration of methotrexate under ultrasonographic guidance., Result(s): Ultrasonographic study revealed a gestational sac in the anterior wall of the uterine isthmus with peritrophoblastic flow. It was treated conservatively and successfully with local methotrexate administration under ultrasonographic guidance., Conclusion(s): The early diagnosis of ectopic cesarean scar pregnancy allows the conservative treatment with local administration of methotrexate under ultrasonographic guidance.