Thymic stromal lymphopoietin (TSLP) has multifaceted immunological functions ranging from maintenance of tolerance to induction of disease. Two human transcript variants of TSLP are described: a long ...form (variant 1; lfTSLP) consisting of four exons and an alternative, short form (variant 2; sfTSLP) that lacks two exons compared with variant 1. SfTSLP has not been described at the protein level or functionally studied. Here, we demonstrate that the human sfTSLP is the predominant form of TSLP, constitutively expressed at the mRNA and protein level in keratinocytes of oral mucosa and skin and in salivary glands, is released in saliva, and is not regulated in the same manner as the long form. Compared with lfTSLP, sfTSLP exhibits a markedly stronger antibacterial activity. Synthetic sfTSLP did not activate signal transducer and activator of transcription 5 (STAT5) signaling in CD1c(+) dendritic cells nor interfered with STAT5 activation by lfTSLP. SfTSLP may, therefore, act as an antimicrobial peptide in the oral cavity and on the skin to create a defense barrier that aids in the control of both commensal and pathogenic microbes. The results show that the two translational products of the TSLP gene have a different expression and different biological properties, and emphasize the importance of analyzing the two TSLP isoforms separately.
Abstract Deep diving mammals have developed strategies to cope with limited oxygen availability when submerged. These adaptations are associated with an increased neuronal hypoxia tolerance. Brain ...neurons of the hooded seal Cystophora cristata remain much longer active in hypoxic conditions than those of mice. To understand the cellular basis of neuronal hypoxia tolerance, we studied neuroglobin and cytochrome c in C. cristata brain. Neuroglobin, a respiratory protein typically found in vertebrate neurons, displays three unique amino acid substitutions in hooded seal. However, these substitutions unlikely contribute to a modulation of O2 affinity. Moreover, there is no significant difference in total neuroglobin protein levels in mouse, rat and seal brains. However, in terrestrial mammals neuroglobin resided exclusively in neurons, whereas in seals neuroglobin is mainly located in astrocytes. This unusual localization of neuroglobin is accompanied by a shift in the distribution of cytochrome c. In seals, this marker for oxidative metabolism is mainly localized in astrocytes, whereas in terrestrial mammals it is essentially found in neurons. Our results indicate that in seals aerobic ATP production depends significantly on astrocytes, while neurons rely less on aerobic energy metabolism. This adaptation may imbue seal neurons with an increased tolerance to hypoxia and potentially also to reactive oxygen species, and may explain in part the ability of deep diving mammals to sustain neuronal activity during prolonged dives.
Streptococcus mitis colonizes all niches of the human oral cavity from early infancy and throughout life. Monocytes patrol blood vessels, lymphoid and non‐lymphoid tissues and migrate into infected ...tissue where they participate in the inflammatory cascade and immune regulation. Here, we studied the effect of S. mitis on monocytes. Transcriptome analysis of monocytes exposed to S. mitis (SmMo) revealed increased transcription of chemotactic factors (CCL2, CCL3, CCL20, CXCL1, CXCL2) and cytokines (IL1A, IL1B, IL6, IL23, IL36G, TNF), indicating that S. mitis may trigger recruitment of leucocytes and initiate inflammation. Increased transcription in SmMo of IL1B, IL6 and IL23 indicated that S. mitis may participate in the induction of Th17 responses and agreed with our earlier findings of S. mitis‐mediated memory Th17 reactivity. Furthermore, S. mitis inhibited tetanus toxoid‐specific CD4 T cell proliferation. This can be due to the increased secretion of IL‐10 and expression of PD‐L1 that was observed in SmMo. PGE2 can modulate IL‐10 and PD‐L1 expression, concomitant with that of CCR7, IL‐12 and IL‐23 that also were changed. This, along with increased SmMo transcription of PTGS2 (COX2) and PTGER4 (EP4), pointed to a role of PGE2. Measurement of PGE2 secretion by SmMo showed indeed a marked increase, and chemical inhibition of PGE2 production lowered the PD‐L1 expression on SmMo. In conclusion, our findings show that S. mitis may trigger immune modulation by recruiting immune cells to the site of infection, while at the same time dampening the severity of the response through expression of IL‐10, PGE2 and PD‐L1.
This systematic scoping review was conducted to 1) identify and describe labor curves that illustrate cervical dilatation over time; 2) map any evidence for, as well as outcomes used to evaluate the ...accuracy and effectiveness of the curves; and 3) identify areas in research that require further investigation.
A three-step systematic literature search was conducted for publications up to May 2023. We searched the Medline, Maternity & Infant Care, Embase, Cochrane Library, Epistemonikos, CINAHL, Scopus, and African Index Medicus databases for studies describing labor curves, assessing their effectiveness in improving birth outcomes, or assessing their accuracy as screening or diagnostic tools. Original research articles and systematic reviews were included. We excluded studies investigating adverse birth outcomes retrospectively, and those investigating the effect of analgesia-related interventions on labor progression. Study eligibility was assessed, and data were extracted from included studies using a piloted charting form. The findings are presented according to descriptive summaries created for the included studies.
Of 26,073 potentially eligible studies, 108 studies were included. Seventy-three studies described labor curves, of which ten of the thirteen largest were based mainly on the United States Consortium on Safe Labor cohort. Labor curve endpoints were 10 cm cervical dilatation in 69 studies and vaginal birth in 4 studies. Labor curve accuracy was assessed in 26 studies, of which all 15 published after 1986 were from low- and middle-income countries. Recent studies of labor curve accuracy in high-income countries are lacking. The effectiveness of labor curves was assessed in 13 studies, which failed to prove the superiority of any curve. Patient-reported health and well-being is an underrepresented outcome in evaluations of labor curves. The usefulness of labor curves is still a matter of debate, as studies have failed to prove their accuracy or effectiveness.
Background
Umbilical cord blood acid–base sampling is routinely performed at many hospitals. Recent studies have questioned this practice and the association of acidosis with cerebral palsy.
...Objective
To investigate the associations between the results of umbilical cord blood acid–base analysis at birth and long‐term neurodevelopmental outcomes and mortality in children.
Search strategy
We searched six databases using the search strategy: umbilical cord AND outcomes.
Selection criteria
Randomised controlled trials, cohorts and case–control studies from high‐income countries that investigated the association between umbilical cord blood analysis and neurodevelopmental outcomes and mortality from 1 year after birth in children born at term.
Data collection and analysis
We critically assessed the included studies, extracted data and conducted meta‐analyses comparing adverse outcomes between children with and without acidosis, and the mean proportions of adverse outcomes. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach.
Main results
We have very low confidence in the following findings: acidosis was associated with higher cognitive development scores compared with non‐acidosis (mean difference 5.18, 95% CI 0.84–9.52; n = two studies). Children with acidosis also showed a tendency towards higher risk of death (relative risk RR 5.72, 95% CI 0.90–36.27; n = four studies) and CP (RR 3.40, 95% CI 0.86–13.39; n = four studies), although this was not statistically significant. The proportion of children with CP was 2.39/1000 across the studies, assessed as high certainty evidence.
Conclusion
Due to low certainty of evidence, the associations between umbilical cord blood gas analysis at delivery and long‐term neurodevelopmental outcomes in children remains unclear.
This article includes Author Insights, a video available at: https://players.brightcove.net/3806881048001/default_default/index.html?videoId=6322480161112.
Background Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their ...effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. Methods The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. Discussion The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. Trial registration ClinicalTrials.gov Identifier: NCT01538550. Keywords: Diet, Lifestyle, Prescription drugs, Gut microbiome, Metagenomics sequencing, Biomarkers, Screening, FIT, iFOBT, Colonoscopy, Adenoma, Colorectal cancer, Advanced neoplasia
Abstract Direct evidence that the mammalian neocortex is an important generator of intrinsic activity comes from isolated neocortical slices that spontaneously generate multiple rhythms including ...those in the beta, delta and gamma range. These oscillations are also seen in intact animals where they interact with other areas including the hippocampus, thalamus and basal ganglia. Here we show that thick isolated neocortical slices from hooded seals intrinsically generate persistent spontaneous activities, both repetitive non-rhythmic activity with activity states lasting for several minutes, and oscillating activity with rhythms that are much slower (<0.1 Hz) than the rhythms previously described in vitro . These intrinsic activities were very robust and persisted for up to 1 h even in severely hypoxic conditions. We hypothesize that the remarkable hypoxia tolerance of the hooded seal nervous system made it possible to maintain functional integrity in slices thick enough to preserve intact neuronal networks capable of generating these slow oscillations. The observed activities in seal neocortical slices support the notion that mammalian cortical networks intrinsically generate multiple states of activity that include oscillatory activity all the way down to <0.1 Hz. This intrinsic neocortical excitability is an important contributor not only to sleep but also to the default awake state of the neocortex.
Understanding the determinants of poorly studied species’ spatial ecology is fundamental to understanding climate change impacts on those species and how to effectively prioritise their conservation. ...Ross seals (
Ommatophoca rossii
) are the least studied of the Antarctic pinnipeds with a limited knowledge of their spatial ecology. We present the largest tracking study for this species to date, create the first habitat models, and discuss the potential impacts of climate change on their preferred habitat and the implications for conservation. We combined newly collected satellite tracking data (2016–2019:
n
= 11) with previously published data (2001:
n
= 8) from the Weddell, King Haakon VII and Lazarev seas, Antarctica, and used 16 remotely sensed environmental variables to model Ross seal habitat suitability by means of boosted regression trees for summer and winter, respectively. Five of the top environmental predictors were relevant in both summer and winter (sea-surface temperature, distance to the ice edge, ice concentration standard deviation, mixed-layer depth, and sea-surface height anomalies). Ross seals preferred to forage in waters ranging between −1 and 2°C, where the mixed-layer depth was shallower in summer and deeper in winter, where current speeds were slower, and away from the ice edge in the open ocean. Receding ice edge and shoaling of the mixed layer induced by climate change may reduce swimming distances and diving depths, thereby reducing foraging costs. However, predicted increased current speeds and sea-surface temperatures may reduce habitat suitability in these regions. We suggest that the response of Ross seals to climate change will be regionally specific, their future success will ultimately depend on how their prey responds to regional climate effects and their own behavioural plasticity.
Pinnipeds rely primarily on oxygen stores in blood and muscles to support aerobic diving; therefore rapid development of body oxygen stores (TBO₂) is crucial for pups to transition from nursing to ...independent foraging. Here, we investigate TBO₂ development in 45 harp (Pagophilus groenlandicus) and 46 hooded (Cystophora cristata) seals ranging in age from neonates to adult females. We found that hooded seal adults have the largest TBO₂ stores yet reported (89.5 ml kg-¹), while harp seal adults have values more similar to other phocids (71.6 ml kg-¹). In adults, large TBO₂ stores resulted from large blood volume (harp169, hood 194 ml kg-¹) and high muscle Mb content (harp 86.0, hood 94.8 mg g-¹). In contrast, pups of both species had significantly lower mass-specific TBO₂ stores than adults, and stores declined rather than increased during the nursing period. This decline was due to a reduction in mass-specific blood volume and the absence of an increase in the low Mb levels (harp 21.0, hood 31.5 mg g-¹). Comparisons with other phocid species suggests that the pattern of blood and muscle development in the pre- and post-natal periods varies with terrestrial period, and that muscle maturation rates may influence the length of the postweaning fast. However, final maturation of TBO₂ stores does not take place until after foraging begins.
Introduction
Women planning a home birth are transferred to hospital in case of complications or elevated risk for adverse outcomes. The aim of the present study was to describe the indications for ...transfer to hospital in planned home births, and the proportion of cases in which this occurs.
Material and methods
Women in Norway, Sweden, Denmark and Iceland who had opted for, and were accepted for, home birth at the onset of labor, were included in the study. Data from 3068 women, 572 nulliparas and 2446 multiparas, were analyzed for proportion of transfers during labor and within 72 h after birth, indications for transfer, how long before or after birth the transfer started, time from birth to start of transfer, duration and mode of transfer, and whether the transfer was classified as potentially urgent. Analyses were stratified for nulliparity and multiparity.
Results
One‐third (186/572) of the nulliparas were transferred to hospital, 137 (24.0%) during labor and 49 (8.6%) after the birth. Of the multiparas, 195/2446 (8.0%) were transferred, 118 (4.8%) during labor and 77 (3.2%) after birth. The most common indication for transfers during labor was slow progress. In transfers after birth, postpartum hemorrhage, tears and neonatal respiratory problems were the most common indications. A total of 116 of the 3068 women had transfers classified as potentially urgent.
Conclusions
One‐third of all nulliparous and 8.0% of multiparous women were transferred during labor or within 72 h of the birth. The proportion of potentially urgent transfers was 3.8%.
PDF
