Physiologically based cord clamping for infants ≥32+0 weeks gestation: A randomised clinical trial and reference percentiles for heart rate and oxygen saturation for infants ≥35+0 weeks gestation

BackgroundGlobally, the majority of newborns requiring resuscitation at birth are full term or late-preterm infants. These infants typically have their umbilical cord clamped early (ECC) before moving to a resuscitation platform, losing the potential support of the placental circulation. Physiologically based cord clamping (PBCC) is clamping the umbilical cord after establishing lung aeration and holds promise as a readily available means of improving early newborn outcomes. In mechanically ventilated lambs, PBCC improved cardiovascular stability and reduced hypoxia. We hypothesised that PBCC compared to ECC would result in higher heart rate (HR) in infants needing resuscitation, without compromising safety.Methods and findingsBetween 4 July 2018 and 18 May 2021, infants born at ≥32⁺⁰ weeks’ gestation with a paediatrician called to attend were enrolled in a parallel-arm randomised trial at 2 Australian perinatal centres. Following initial stimulation, infants requiring further resuscitation were randomised within 60 seconds of birth using a smartphone-accessible web link. The intervention (PBCC) was to establish lung aeration, either via positive pressure ventilation (PPV) or effective spontaneous breathing, prior to cord clamping. The comparator was early cord clamping (ECC) prior to resuscitation. The primary outcome was mean HR between 60 to 120 seconds after birth, measured using 3-lead electrocardiogram, extracted from video recordings blinded to group allocation. Nonrandomised infants had deferred cord clamping (DCC) ≥120 seconds in the observational study arm.Among 508 at-risk infants enrolled, 123 were randomised (n = 63 to PBCC, n = 60 to ECC). Median (interquartile range, IQR) for gestational age was 39.9 (38.3 to 40.7) weeks in PBCC infants and 39.6 (38.4 to 40.4) weeks in ECC infants. Approximately 49% and 50% of the PBCC and ECC infants were female, respectively. Five infants (PBCC = 2, ECC = 3, 4% total) had missing primary outcome data. Cord clamping occurred at a median (IQR) of 136 (126 to 150) seconds in the PBCC arm and 37 (27 to 51) seconds in the ECC arm. Mean HR between 60 to 120 seconds after birth was 154 bpm (beats per minute) for PBCC versus 158 bpm for ECC (adjusted mean difference −6 bpm, 95% confidence interval (CI) −17 to 5 bpm, P = 0.39). Among 31 secondary outcomes, postpartum haemorrhage ≥500 ml occurred in 34% and 32% of mothers in the PBCC and ECC arms, respectively. Two hundred ninety-five nonrandomised infants (55% female) with median (IQR) gestational age of 39.6 (38.6 to 40.6) weeks received DCC. Data from these infants was used to create percentile charts of expected HR and oxygen saturation in vigorous infants receiving DCC. The trial was limited by the small number of infants requiring prolonged or advanced resuscitation. PBCC may provide other important benefits we did not measure, including improved maternal–infant bonding and higher iron stores.ConclusionsIn this study, we observed that PBCC resulted in similar mean HR compared to infants receiving ECC. The findings suggest that for infants ≥32⁺⁰ weeks’ gestation who receive brief, effective resuscitation at closely monitored births, PBCC does not provide additional benefit over ECC (performed after initial drying and stimulation) in terms of key physiological markers of transition. PBCC was feasible using a simple, low-cost strategy at both cesarean and vaginal births. The percentile charts of HR and oxygen saturation may guide clinicians monitoring the transition of at-risk infants who receive DCC.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000621213.

Shiraz Badurdeen and colleagues evaluate whether physiologically-based cord clamping provides physiological benefits over early cord clamping for infants requiring resuscitation at birth.     

Fast classification and compositional analysis of cornstover fractions using Fourier transform near-infrared techniques

The objectives of this research were to determine the variation of chemical composition across botanical fractions of cornstover, and to probe the potential of Fourier transform near-infrared (FT-NIR) techniques in qualitatively classifying separated cornstover fractions and in quantitatively analyzing chemical compositions of cornstover by developing calibration models to predict chemical compositions of cornstover based on FT-NIR spectra. Large variations of cornstover chemical composition for wide calibration ranges, which is required by a reliable calibration model, were achieved by manually separating the cornstover samples into six botanical fractions, and their chemical compositions were determined by conventional wet chemical analyses, which proved that chemical composition varies significantly among different botanical fractions of cornstover. Different botanic fractions, having total saccharide content in descending order, are husk, sheath, pith, rind, leaf, and node. Based on FT-NIR spectra acquired on the biomass, classification by Soft Independent Modeling of Class Analogy (SIMCA) was employed to conduct qualitative classification of cornstover fractions, and partial least square (PLS) regression was used for quantitative chemical composition analysis. SIMCA was successfully demonstrated in classifying botanical fractions of cornstover. The developed PLS model yielded root mean square error of prediction (RMSEP %w/w) of 0.92, 1.03, 0.17, 0.27, 0.21, 1.12, and 0.57 for glucan, xylan, galactan, arabinan, mannan, lignin, and ash, respectively. The results showed the potential of FT-NIR techniques in combination with multivariate analysis to be utilized by biomass feedstock suppliers, bioethanol manufacturers, and bio-power producers in order to better manage bioenergy feedstocks and enhance bioconversion.     

Protein kinases display minimal interpositional dependence on substrate sequence: potential implications for the evolution of signalling networks

Characterization of in vitro substrates of protein kinases by peptide library screening provides a wealth of information on the substrate specificity of kinases for amino acids at particular positions relative to the site of phosphorylation, but provides no information concerning interdependence among positions. High-throughput techniques have recently made it feasible to identify large numbers of in vivo kinase substrates. We used data from experiments on the kinases ATM/ATR and CDK1, and curated CK2 substrates to evaluate the prevalence of interactions between substrate positions within a motif and the utility of these interactions in predicting kinase substrates. Among these data, evidence of interpositional sequence dependencies is strikingly rare, and what dependency exists does little to aid in the prediction of novel kinase substrates. Significant increases in the ability of models to predict kinase-substrate specificity beyond position-independent models must come largely from inclusion of elements of biological and cellular context, rather than further analysis of substrate sequences alone. Our results suggest that, evolutionarily, kinase substrate fitness exists in a smooth energetic landscape. Taken with results from others indicating that phosphopeptide-binding domains do exhibit interpositional dependence, our data suggest that incorporation of new substrate molecules into phospho-signalling networks may be rate-limited by the evolution of suitability for binding by phosphopeptide-binding domains.     

Diurnal variability in a fish assemblage of a Bahamian coral reef

Synopsis Variation in the diurnal composition of a fish assemblage of a Bahamian coral reef was investigated by comparing visual counts of fishes taken along a 100 × 4 m wide fixed transect at four times: 0900, 1200, 1500 and 1800 hours during the summer of 1979. One sample per day was obtained at each time period over a span of 20 consecutive days. Forty-two species were recorded in these samples, with 25 occurring frequently enough to permit statistical analysis of diurnal variations in abundance. Of the 25 species compared, nearly one fourth (6 species) displayed significant variation in abundance patterns among the four time periods tested. It is suggested, because of the strong possibility of bias which might otherwise be introduced because of these variations, that repetitive quantitative visual censusing of coral reef fishes be undertaken at about the same time each day.     

Programmed cell death in neurotumour cells involves the generation of ceramide

Ceramide has been typically thought of as the membrane anchor for the carbohydrate in glycosphingolipids but many studies have suggested that it may cause apoptosis. Apoptosis or programmed cell death (PCD) is thought to be responsible for the death of one-half of neurons surviving the development of the nervous system. The potential involvement of the sphingomyelin-ceramide signaling process as an integral part of PCD was therefore examined in several neurotumour cell lines. We show that synthetic C2-ceramide (N-acetylsphingosine), a soluble ceramide analogue, can rapidly trigger PCD in these cells, characterized by: 1) classic DNA laddering on agarose gels; 2) DNA fragmentation as determined by Hoechst Dye; and 3) cell viability (mitochondrial function and intact nuclei) assays. We report that staurosporine can both activate PCD (by all three criteria above) in neurotumour cells and increase both the formation of ceramide and ceramide mass. Both ceramide formation and the induction of PCD were further enhanced by the co-addition of a ceramidase inhibitor oleoylethanolamine (25 µM). Staurosporine and oleoylethanolamine were similarly effective in inducing ceramide formation and PCD in immortalized hippocampal neurons (HN-2) and immortalized dorsal root ganglion cells (F-11). Our data suggests that formation of ceramide is a key event in the induction of PCD in neuronally derived neurotumour cells.Abbreviations PCD programmed cell death - PKC protein kinase C - HPTLC high-performance thin-layer chromatography - DETAPAC diethylenetriaminepentaacetic acid - DMEM Dubelco's modified Eagle's medium - FCS fetal calf serum - PBS phosphate-buffered saline - DAG diacylglycerol - DDI distilled-deionized - Cer ceramide - SM sphingomyelin Dedicated to Dr Sen-itiroh Hakomori in celebration of his 65th birthday.     

Reproducibility of swallow-induced cortical BOLD positive and negative fMRI activity

Functional MRI (fMRI) studies have demonstrated that a number of brain regions (cingulate, insula, prefrontal, and sensory/motor cortices) display blood oxygen level-dependent (BOLD) positive activity during swallow. Negative BOLD activations and reproducibility of these activations have not been systematically studied. The aim of our study was to investigate the reproducibility of swallow-related cortical positive and negative BOLD activity across different fMRI sessions. We studied 16 healthy volunteers utilizing an fMRI event-related analysis. Individual analysis using a general linear model was used to remove undesirable signal changes correlated with motion, white matter, and cerebrospinal fluid. The group analysis used a mixed-effects multilevel model to identify active cortical regions. The volume and magnitude of a BOLD signal within each cluster was compared between the two study sessions. All subjects showed significant clustered BOLD activity within the known areas of cortical swallowing network across both sessions. The cross-correlation coefficient of percent fMRI signal change and the number of activated voxels across both positive and negative BOLD networks were similar between the two studies (r ≥ 0.87, P < 0.0001). Swallow-associated negative BOLD activity was comparable to the well-defined "default-mode" network, and positive BOLD activity had noticeable overlap with the previously described "task-positive" network. Swallow activates two parallel cortical networks. These include a positive and a negative BOLD network, respectively, correlated and anticorrelated with swallow stimulus. Group cortical activity maps, as well as extent and amplitude of activity induced by volitional swallowing in the cortical swallowing network, are reproducible between study sessions.     

The rumen anaerobic fungi

The anaerobic fungi represent a new group of organisms inhabiting the rumen ecosystem and possess a life cycle alternating between a motile flagellated form (zoospore) and a non-motile vegetative reproductive form (thallus). In vivo studies show extensive colonization of plant material suspended in the rumen indicating the fungi have a role in fiber digestion. Pure cultures of anaerobic fungi ferment cellulose to give lactate, acetate, CO₂ and H₂ as the major products. Ethanol and formate may also be produced. Fermentation of cellulose by the fungi in coculture with H₂-utilizing methanogens results in a shift in the fermentation pattern favouring the production of H₂ (utilized in the formation of CH₄) and acetate at the expense of the electron-sink products, lactate and ethanol. It is postulated that the methanogens in reducing the partial pressure of H₂, facilitate an increased passage of reducing equivalents towards the production of H₂ via a pyridine-nucleotide (PN)-linked hydrogenase reaction. H₂ is believed to be produced in microbodies of the fungi called hydrogenosomes which possess all of the enzymes necessary for this function including PN-linked hydrogenase. Absence of mitochondria and key electron transport components in these organisms indicate a dependence wholly on fermentative processes for growth. Anaerobic fungi also participate in hemicellulose and starch degredation but it is not yet clear whether they have a role in the degradation of lignin. Simple sugars (mono- and disaccharides) are readily utilized and their uptake is subject to similar regulatory constraints such as is found with other micro-organisms.Enzymological studies have revealed that anaerobic fungi release substantial amounts of endo-acting cellulase and protease, possibly giving them a competitive advantage over rumen bacteria in the degradation of plant structural material.     

Mitotic checkpoint gene expression is tuned by codon usage bias

The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Correct functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about the regulation of SAC gene expression. Here, we show in the fission yeast Schizosaccharomyces pombe that a combination of short mRNA half‐lives and long protein half‐lives supports stable SAC protein levels. For the SAC genes mad2 ⁺ and mad3 ⁺, their short mRNA half‐lives are caused, in part, by a high frequency of nonoptimal codons. In contrast, mad1 ⁺ mRNA has a short half‐life despite a higher frequency of optimal codons, and despite the lack of known RNA‐destabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co‐translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine‐tuned to ensure proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.