Premature birth (before 37 weeks of gestation) has been linked to a variety of adverse neurological outcomes. Sleep problems are associated with decreased neurocognitive functioning, which is ...especially common in children born preterm. The exact relationship between prematurity and sleep at school age is unknown. A systematic review is performed with the aim to assess the relationship between prematurity and sleep at school age (5th to 18th year of life), in comparison to sleep of their peers born full-term. Of 347 possibly eligible studies, nine were included. The overall conclusion is that prematurity is associated with earlier bedtimes and a lower sleep quality, in particular more nocturnal awakenings and more non-rapid eye movement stage 2 sleep. Interpretations and limitations of the review are discussed. Moreover, suggestions for future research are brought forward, including the need for a systematic approach with consistent outcome measures in this field of research. A better understanding of the mechanisms that influence sleep in the vulnerable group of children born preterm could help optimize these children's behavioral and intellectual development.
Sleep is paramount for optimal brain development in infants admitted to the neonatal intensive care unit. Besides (minimally) invasive technical approaches to study sleep in infants, there is ...currently a large variety of behavioral sleep stage classification methods (BSSCs) that can be used to identify sleep stages in preterm infants born <37 weeks gestational age. However, they operate different criteria to define sleep stages, which limits the comparability and reproducibility of research on preterm sleep. This scoping review aims to: 1) identify and elaborate on existing neonatal BSSCs used for preterm infants, 2) examine the reliability and validity of these BSSCs, and 3) identify which criteria are most used for different ages, ranging from 23 to 37 weeks postmenstrual age at observation.
To map the existing BSSCs, PubMed, EMBASE and Cochrane were searched for studies using a BSSC to identify sleep stages in preterm infants.
In total, 36 BSSCs were identified with on average five item categories assessed per BSSC, most frequently: eyes, body movements, facial movements, sounds, and respiratory pattern. Furthermore, validity and reliability of the BSSCs were tested in less than half of the included studies. Finally, BSSCs were used in infants of all ages, regardless the age for which the BSSC was originally developed.
Items used for scoring in the different BSSCs were relatively consistent. The age ranges, reliability, and validity of the BSSCs were not consistently reported in most studies. Either validation studies of existing BSSCs or new BSSCs are necessary to improve the comparability and reproducibility of previous and future preterm behavioral sleep studies.
•Preterm sleep stages can be assessed using behavioral classification methods (BSSCs).•Many BSSCs used in preterm infants are originally developed for term infants.•Validity and reliability are not consistently reported in BSSCs used in preterm infants.•Validated BSSCs are necessary to improve reproducibility of preterm sleep studies.•Most BSSCs comprised five frequently recurring categories of scoring items.
Temporal flooding is a common environmental stress for terrestrial plants. Aquatic adventitious roots (aquatic roots) are commonly formed in flooding-tolerant plant species and are generally assumed ...to be beneficial for plant growth by supporting water and nutrient uptake during partial flooding. However, the actual contribution of these roots to plant performance under flooding has hardly been quantified. As the investment into aquatic root development in terms of carbohydrates may be costly, these costs may - depending on the specific environmental conditions - offset the beneficial effects of aquatic roots. This study tested the hypothesis that the balance between potential costs and benefits depends on the duration of flooding, as the benefits are expected to outweigh the costs in long-term but not in short-term flooding.
The contribution of aquatic roots to plant performance was tested in Solanum dulcamara during 1-4 weeks of partial submergence and by experimentally manipulating root production. Nutrient uptake by aquatic roots, transpiration and photosynthesis were measured in plants differing in aquatic root development to assess the specific function of these roots.
As predicted, flooded plants benefited from the presence of aquatic roots. The results showed that this was probably due to the contribution of roots to resource uptake. However, these beneficial effects were only present in long-term but not in short-term flooding. This relationship could be explained by the correlation between nutrient uptake and the flooding duration-dependent size of the aquatic root system.
The results indicate that aquatic root formation is likely to be selected for in habitats characterized by long-term flooding. This study also revealed only limited costs associated with adventitious root formation, which may explain the maintenance of the ability to produce aquatic roots in habitats characterized by very rare or short flooding events.
Highlights • Novel liposome based adjuvant formulation CAF01 safe in first-in-human clinical trial. • H1 antigen + CAF01 adjuvant induce T-cell responses in human. • T-cell immunity is very ...long-lasting, specific responses detectable up to 150 weeks.
Highlights • H4:IC31 vaccination was well tolerated with an acceptable safety profile. • H4:IC31 vaccination elicited persistent antigen-specific CD4+ T cell responses. • H4:IC31 triggered T cell ...expansion, IFNγ production and multifunctional Th1 cells. • Optimal antigen-adjuvant doses were 5, 15, or 50 μg of H4 plus 500 nmol of IC31.
Dendritic cells (DCs) present foreign antigen in major histocompatibility complex (MHC) class I molecules to cytotoxic T cells in a process called cross-presentation. An important step in this ...process is the release of antigen from the lumen of endosomes into the cytosol, but the mechanism of this step is still unclear. In this study, we show that reactive oxygen species (ROS) produced by the NADPH-oxidase complex NOX2 cause lipid peroxidation, a membrane disrupting chain-reaction, which in turn results in antigen leakage from endosomes. Antigen leakage and cross-presentation were inhibited by blocking ROS production or scavenging radicals and induced when using a ROS-generating photosensitizer. Endosomal antigen release was impaired in DCs from chronic granulomatous disease (CGD) patients with dysfunctional NOX2. Thus, NOX2 induces antigen release from endosomes for cross-presentation by direct oxidation of endosomal lipids. This constitutes a new cellular function for ROS in regulating immune responses against pathogens and cancer.
Cells sense the extracellular environment and mechanical stimuli and translate these signals into intracellular responses through mechanotransduction, which alters cell maintenance, proliferation, ...and differentiation. Here we use a mouse model of trauma-induced heterotopic ossification (HO) to examine how cell-extrinsic forces impact mesenchymal progenitor cell (MPC) fate. After injury, single-cell (sc) RNA sequencing of the injury site reveals an early increase in MPC genes associated with pathways of cell adhesion and ECM-receptor interactions, and MPC trajectories to cartilage and bone. Immunostaining uncovers active mechanotransduction after injury with increased focal adhesion kinase signaling and nuclear translocation of transcriptional coactivator TAZ, inhibition of which mitigates HO. Similarly, joint immobilization decreases mechanotransductive signaling, and completely inhibits HO. Joint immobilization decreases collagen alignment and increases adipogenesis. Further, scRNA sequencing of the HO site after injury with or without immobilization identifies gene signatures in mobile MPCs correlating with osteogenesis, and signatures from immobile MPCs with adipogenesis. scATAC-seq in these same MPCs confirm that in mobile MPCs, chromatin regions around osteogenic genes are open, whereas in immobile MPCs, regions around adipogenic genes are open. Together these data suggest that joint immobilization after injury results in decreased ECM alignment, altered MPC mechanotransduction, and changes in genomic architecture favoring adipogenesis over osteogenesis, resulting in decreased formation of HO.
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