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Trials Jul 2024Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant... (Comparative Study)
Comparative Study Randomized Controlled Trial
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 24-27 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 to 25 weeks or 26 to 27 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 24-27 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.
Topics: Humans; Respiratory Distress Syndrome, Newborn; Infant, Newborn; Pulmonary Surfactants; Infant, Premature; Treatment Outcome; Gestational Age; Continuous Positive Airway Pressure; Bronchopulmonary Dysplasia; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Time Factors; Airway Extubation; Intubation, Intratracheal; Female
PubMed: 38956676
DOI: 10.1186/s13063-024-08240-4 -
International Breastfeeding Journal Jul 2024Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants.
BACKGROUND
Limited research has explored the associations of gestational age (GA) and breastfeeding practices with growth and nutrition in term infants.
METHODS
This multicenter cross-sectional study recruited 7299 singleton term infants from well-child visits in Shandong, China, between March 2021 and November 2022. Data on GA, gender, ethnicity, birth weight, parental heights, gestational diabetes and hypertension, age at visit, breastfeeding practices (point-in-time data at visit for infants < 6 months and retrospective data at 6 months for infants ≥ 6 months), complementary foods introduction, infant length and weight, were collected. 7270 infants were included in the analysis after excluding outliers with Z-scores of length (LAZ), weight or weight for length (WLZ) <-4 or > 4. Linear regression models adjused for covariates explored the impact of GA and breastfeeding practices on LAZ and WLZ, while logistic regression models evaluated their effect on the likelihood of moderate and severe stunting (MSS, LAZ<-2), moderate and severe acute malnutrition (MSAM, WLZ<-2) and overweight/obesity (WLZ > 2). Sensitivity analysis was conducted on normal birth weight infants (2.5-4.0 kg).
RESULTS
Infants born early-term and exclusively breastfed accounted for 31.1% and 66.4% of the sample, respectively. Early-term birth related to higher WLZ (< 6 months: β = 0.23, 95% confidence interval (CI): 0.16, 0.29; ≥6 months: β = 0.12, 95% CI: 0.04, 0.20) and an increased risk of overweight/obesity throughout infancy (< 6 months: OR: 1.41, 95% CI 1.08, 1.84; ≥6 months: OR: 1.35, 95% CI 1.03, 1.79). Before 6 months, early-term birth correlated with lower LAZ (β=-0.16, 95% CI: -0.21, -0.11) and an increased risk of MSS (OR: 1.01, 95%CI 1.00, 1.02); Compared to exclusive breastfeeding, exclusive formula-feeding and mixed feeding linked to lower WLZ (β=-0.15, 95%CI -0.30, 0.00 and β=-0.12, 95%CI -0.19, -0.05, respectively) and increased risks of MSAM (OR: 5.57, 95%CI 1.95, 15.88 and OR: 3.19, 95%CI 1.64, 6.19, respectively). Sensitivity analyses confirmed these findings.
CONCLUSIONS
The findings emphasize the health risks of early-term birth and the protective effect of exclusive breastfeeding in singleton term infants, underscoring the avoidance of nonmedically indicated delivery before 39 weeks and promoting exclusive breastfeeding before 6 months.
Topics: Humans; Breast Feeding; Cross-Sectional Studies; Female; Male; Infant, Newborn; Infant; China; Gestational Age; Infant Nutritional Physiological Phenomena; Term Birth; Retrospective Studies; Adult; Nutritional Status
PubMed: 38956574
DOI: 10.1186/s13006-024-00653-w -
BMC Genomics Jul 2024Oil bodies or lipid droplets (LDs) in the cytosol are the subcellular storage compartments of seeds and the sites of lipid metabolism providing energy to the germinating...
BACKGROUND
Oil bodies or lipid droplets (LDs) in the cytosol are the subcellular storage compartments of seeds and the sites of lipid metabolism providing energy to the germinating seeds. Major LD-associated proteins are lipoxygenases, phospholipaseD, oleosins, TAG-lipases, steroleosins, caleosins and SEIPINs; involved in facilitating germination and enhancing peroxidation resulting in off-flavours. However, how natural selection is balancing contradictory processes in lipid-rich seeds remains evasive. The present study was aimed at the prediction of selection signatures among orthologous clades in major oilseeds and the correlation of selection effect with gene expression.
RESULTS
The LD-associated genes from the major oil-bearing crops were analyzed to predict natural selection signatures in phylogenetically close-knit ortholog clusters to understand adaptive evolution. Positive selection was the major force driving the evolution and diversification of orthologs in a lineage-specific manner. Significant positive selection effects were found in 94 genes particularly in oleosin and TAG-lipases, purifying with excess of non-synonymous substitution in 44 genes while 35 genes were neutral to selection effects. No significant selection impact was noticed in Brassicaceae as against LOX genes of oil palm. A heavy load of deleterious mutations affecting selection signatures was detected in T-lineage oleosins and LOX genes of Arachis hypogaea. The T-lineage oleosin genes were involved in mainly anther, tapetum and anther wall morphogenesis. In Ricinus communis and Sesamum indicum > 85% of PLD genes were under selection whereas selection pressures were low in Brassica juncea and Helianthus annuus. Steroleosin, caleosin and SEIPINs with large roles in lipid droplet organization expressed mostly in seeds and were under considerable positive selection pressures. Expression divergence was evident among paralogs and homeologs with one gene attaining functional superiority compared to the other. The LOX gene Glyma.13g347500 associated with off-flavor was not expressed during germination, rather its paralog Glyma.13g347600 showed expression in Glycine max. PLD-α genes were expressed on all the tissues except the seed,δ genes in seed and meristem while β and γ genes expressed in the leaf.
CONCLUSIONS
The genes involved in seed germination and lipid metabolism were under strong positive selection, although species differences were discernable. The present study identifies suitable candidate genes enhancing seed oil content and germination wherein directional selection can become more fruitful.
Topics: Selection, Genetic; Lipid Droplets; Evolution, Molecular; Crops, Agricultural; Phylogeny; Plant Proteins; Plant Oils; Seeds; Gene Expression Regulation, Plant
PubMed: 38956471
DOI: 10.1186/s12864-024-10527-4 -
Scientific Reports Jul 2024Environmental temperature strongly influences the adaptation dynamics of amphibians, whose limited regulation capabilities render them susceptible to thermal...
Environmental temperature strongly influences the adaptation dynamics of amphibians, whose limited regulation capabilities render them susceptible to thermal oscillations. A central element of the adaptive strategies is the transcription factors (TFs), which act as master regulators that orchestrate stress responses, enabling species to navigate the fluctuations of their environment skillfully. Our study delves into the intricate relationship between TF expression and thermal adaptation mechanisms in the Rhinella spinulosa populations. We sought to elucidate the dynamic modulations of TF expression in prometamorphic and metamorphic tadpoles that inhabit two thermally contrasting environments (Catarpe and El Tatio Geyser, Chile) and which were exposed to two thermal treatments (25 °C vs. 20 °C). Our findings unravel an intriguing dichotomy in response strategies between these populations. First, results evidence the expression of 1374 transcription factors. Regarding the temperature shift, the Catarpe tadpoles show a multifaceted approach by up-regulating crucial TFs, including fosB, atf7, and the androgen receptor. These dynamic regulatory responses likely underpin the population's ability to navigate thermal fluctuations effectively. In stark contrast, the El Tatio tadpoles exhibit a more targeted response, primarily up-regulating foxc1. This differential expression suggests a distinct focus on specific TFs to mitigate the effects of temperature variations. Our study contributes to understanding the molecular mechanisms governing thermal adaptation responses and highlights the resilience and adaptability of amphibians in the face of ever-changing environmental conditions.
Topics: Animals; Transcription Factors; Temperature; Larva; Adaptation, Physiological; Bufonidae; Anura; Acclimatization; Chile
PubMed: 38956427
DOI: 10.1038/s41598-024-66127-5 -
Scientific Data Jul 2024Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the...
Teratoma, due to its remarkable ability to differentiate into multiple cell lineages, is a valuable model for studying human embryonic development. The similarity of the gene expression and chromatin accessibility patterns in these cells to those observed in vivo further underscores its potential as a research tool. Notably, teratomas derived from human naïve (pre-implantation epiblast-like) pluripotent stem cells (PSCs) have larger embryonic cell diversity and contain extraembryonic lineages, making them more suitable to study developmental processes. However, the cell type-specific epigenetic profiles of naïve PSC teratomas have not been yet characterized. Using single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), we analyzed 66,384 cell profiles from five teratomas derived from human naïve PSCs and their post-implantation epiblast-like (primed) counterparts. We observed 17 distinct cell types from both embryonic and extraembryonic lineages, resembling the corresponding cell types in human fetal tissues. Additionally, we identified key transcription factors specific to different cell types. Our dataset provides a resource for investigating gene regulatory programs in a relevant model of human embryonic development.
Topics: Humans; Teratoma; Pluripotent Stem Cells; Chromatin; Single-Cell Analysis; Cell Lineage; Transcription Factors
PubMed: 38956385
DOI: 10.1038/s41597-024-03558-9 -
Scientific Reports Jul 2024The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the...
The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the severity, whether in complexity or lethality, significantly influences parental decisions concerning abortion. However, questions remain as to how fetal heart disease severity impacts parental decisions, given recent advancements in postsurgical outcomes. Therefore, we investigated risk factors associated with parents' decision-making regarding abortion following a prenatal diagnosis of fetal heart disease. Our analysis included 73 (terminated: n = 37; continued: n = 36) pregnancies with a fetal heart disease diagnosed before 22 weeks of gestation. Increased gestational age at diagnosis reduced the likelihood of parents' decision on termination (Model 1: adjusted odds ratio, 0.94; 95% confidence interval 0.89-0.99; Model 2: 0.95 0.90-0.997). Critical disease (5.25; 1.09-25.19) and concurrent extracardiac or genetic abnormalities (Model 1: 4.19, 1.21-14.53; Model 2: 5.47, 1.50-19.96) increased the likelihood of choosing abortion. Notably, complex disease did not significantly influence parental decisions (0.56; 0.14-2.20). These results suggest that parental decision-making regarding abortion may be influenced by earlier gestational age at diagnosis, the lethality of heart disease, and extracardiac or genetic abnormalities, but not its complexity if prenatal diagnosis and parental counseling are provided at a cardiovascular-specialized facility.
Topics: Humans; Female; Pregnancy; Abortion, Induced; Decision Making; Adult; Parents; Prenatal Diagnosis; Gestational Age; Heart Defects, Congenital; Heart Diseases; Risk Factors; Fetal Diseases; Male; Severity of Illness Index
PubMed: 38956291
DOI: 10.1038/s41598-024-66027-8 -
Scientific Data Jul 2024Calcification and biomass production by planktonic marine organisms influences the global carbon cycle and fuels marine ecosystems. The major calcifying plankton group...
Calcification and biomass production by planktonic marine organisms influences the global carbon cycle and fuels marine ecosystems. The major calcifying plankton group coccolithophores are highly diverse, comprising ca. 250-300 extant species. However, coccolithophore size (a key functional trait) and degree of calcification are poorly quantified, as most of our understanding of this group comes from a small number of species. We generated a novel reference dataset of coccolithophore morphological traits, including cell-specific data for coccosphere and cell size, coccolith size, number of coccoliths per cell, and cellular calcite content. This dataset includes observations from 1074 individual cells and represents 61 species from 25 genera spanning equatorial to temperate coccolithophore populations that were sampled during the Atlantic Meridional Transect (AMT) 14 cruise in 2004. This unique dataset can be used to explore relationships between morphological traits (cell size and cell calcite) and environmental conditions, investigate species-specific and community contributions to pelagic carbonate production, export and plankton biomass, and inform and validate coccolithophore representation in marine ecosystem and biogeochemical models.
Topics: Atlantic Ocean; Haptophyta; Plankton; Biomass; Calcification, Physiologic; Calcium Carbonate; Ecosystem
PubMed: 38956105
DOI: 10.1038/s41597-024-03544-1 -
Scientific Reports Jul 2024To describe the fetal death rate of birth defects (including a broad range of specific defects) and to explore the relationship between fetal deaths from birth defects...
To describe the fetal death rate of birth defects (including a broad range of specific defects) and to explore the relationship between fetal deaths from birth defects and a broad range of demographic characteristics. Data was derived from the birth defects surveillance system in Hunan Province, China, 2016-2020. Fetal death refers to the intrauterine death of a fetus at any time during the pregnancy, including medical termination of pregnancy. Fetal death rate is the number of fetal deaths per 100 births (including live births and fetal deaths) in a specified group (unit: %). The fetal death rate of birth defects with 95% confidence intervals (CI) was calculated by the log-binomial method. Crude odds ratios (ORs) were calculated to examine the relationship between each demographic characteristic and fetal deaths from birth defects. This study included 847,755 births, and 23,420 birth defects were identified. A total of 11,955 fetal deaths from birth defects were identified, with a fetal death rate of 51.05% (95% CI 50.13-51.96). 15.78% (1887 cases) of fetal deaths from birth defects were at a gestational age of < 20 weeks, 59.05% (7059 cases) were at a gestational age of 20-27 weeks, and 25.17% (3009 cases) were at a gestational age of ≥ 28 weeks. Fetal death rate of birth defects was higher in females than in males (OR = 1.25, 95% CI 1.18-1.32), in rural than in urban areas (OR = 1.43, 95% CI 1.36-1.50), in maternal age 20-24 years (OR = 1.35, 95% CI 1.25-1.47), and ≥ 35 years (OR = 1.19, 95% CI 1.11-1.29) compared to maternal age of 25-29 years, in diagnosed by chromosomal analysis than ultrasound (OR = 6.24, 95% CI 5.15-7.55), and lower in multiple births than in singletons (OR = 0.41, 95% CI 0.36-0.47). The fetal death rate of birth defects increased with the number of previous pregnancies (χ = 49.28, P < 0.01), and decreased with the number of previous deliveries (χ = 4318.91, P < 0.01). Many fetal deaths were associated with birth defects. We found several demographic characteristics associated with fetal deaths from birth defects, which may be related to the severity of the birth defects, economic and medical conditions, and parental attitudes toward birth defects.
Topics: Humans; China; Female; Congenital Abnormalities; Pregnancy; Adult; Fetal Death; Male; Gestational Age; Infant, Newborn; Young Adult; Maternal Age; Odds Ratio
PubMed: 38956101
DOI: 10.1038/s41598-024-65985-3 -
Nature Communications Jul 2024The meninges are critical for the brain functions, but the diversity of meningeal cell types and intercellular interactions have yet to be thoroughly examined. Here we...
The meninges are critical for the brain functions, but the diversity of meningeal cell types and intercellular interactions have yet to be thoroughly examined. Here we identify a population of meningeal lymphatic supporting cells (mLSCs) in the zebrafish leptomeninges, which are specifically labeled by ependymin. Morphologically, mLSCs form membranous structures that enwrap the majority of leptomeningeal blood vessels and all the mural lymphatic endothelial cells (muLECs). Based on its unique cellular morphologies and transcriptional profile, mLSC is characterized as a unique cell type different from all the currently known meningeal cell types. Because of the formation of supportive structures and production of pro-lymphangiogenic factors, mLSCs not only promote muLEC development and maintain the dispersed distributions of muLECs in the leptomeninges, but also are required for muLEC regeneration after ablation. This study characterizes a newly identified cell type in leptomeninges, mLSC, which is required for muLEC development, maintenance, and regeneration.
Topics: Animals; Zebrafish; Meninges; Endothelial Cells; Zebrafish Proteins; Lymphatic Vessels; Animals, Genetically Modified; Lymphangiogenesis; Regeneration
PubMed: 38956047
DOI: 10.1038/s41467-024-49818-5 -
International Journal of Oral Science Jul 2024Apical periodontitis (AP) is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth (i.e., dental pulp tissue),...
Apical periodontitis (AP) is a dental-driven condition caused by pathogens and their toxins infecting the inner portion of the tooth (i.e., dental pulp tissue), resulting in inflammation and apical bone resorption affecting 50% of the worldwide population, with more than 15 million root canals performed annually in the United States. Current treatment involves cleaning and decontaminating the infected tissue with chemo-mechanical approaches and materials introduced years ago, such as calcium hydroxide, zinc oxide-eugenol, or even formalin products. Here, we present, for the first time, a nanotherapeutics based on using synthetic high-density lipoprotein (sHDL) as an innovative and safe strategy to manage dental bone inflammation. sHDL application in concentrations ranging from 25 µg to 100 µg/mL decreases nuclear factor Kappa B (NF-κB) activation promoted by an inflammatory stimulus (lipopolysaccharide, LPS). Moreover, sHDL at 500 µg/mL concentration markedly decreases in vitro osteoclastogenesis (P < 0.001), and inhibits IL-1α (P = 0.027), TNF-α (P = 0.004), and IL-6 (P < 0.001) production in an inflammatory state. Notably, sHDL strongly dampens the Toll-Like Receptor signaling pathway facing LPS stimulation, mainly by downregulating at least 3-fold the pro-inflammatory genes, such as Il1b, Il1a, Il6, Ptgs2, and Tnf. In vivo, the lipoprotein nanoparticle applied after NaOCl reduced bone resorption volume to (1.3 ± 0.05) mm and attenuated the inflammatory reaction after treatment to (1 090 ± 184) cells compared to non-treated animals that had (2.9 ± 0.6) mm (P = 0.012 3) and (2 443 ± 931) cells (P = 0.004), thus highlighting its promising clinical potential as an alternative therapeutic for managing dental bone inflammation.
Topics: Animals; Lipoproteins, HDL; Periapical Periodontitis; NF-kappa B; Mice; Lipopolysaccharides; Osteogenesis; Humans; Osteoclasts; Nanoparticles
PubMed: 38956025
DOI: 10.1038/s41368-024-00316-w