IL-1ß Impacts Vascular Integrity and Lymphatic Function in the Embryonic Omentum.

BACKGROUND: The chromatin-remodeling enzyme BRG1 (brahma-related gene 1) regulates gene expression in a variety of rapidly differentiating cells during embryonic development. However, the critical genes that BRG1 regulates during lymphatic vascular development are unknown. METHODS: We used genetic and imaging techniques to define the role of BRG1 in murine embryonic lymphatic development, although this approach inadvertently expanded our study to multiple interacting cell types. RESULTS: We found that omental macrophages fine-tune an unexpected developmental process by which erythrocytes escaping from naturally discontinuous omental blood vessels are collected by nearby lymphatic vessels. Our data indicate that circulating fibrin(ogen) leaking from gaps in omental blood vessels can trigger inflammasome-mediated IL-1ß (interleukin-1ß) production and secretion from nearby macrophages. IL-1ß destabilizes adherens junctions in omental blood and lymphatic vessels, contributing to both extravasation of erythrocytes and their uptake by lymphatics. BRG1 regulates IL-1ß production in omental macrophages by transcriptionally suppressing the inflammasome trigger RIPK3 (receptor interacting protein kinase 3). CONCLUSIONS: Genetic deletion of Brg1 in embryonic macrophages leads to excessive IL-1ß production, erythrocyte leakage from blood vessels, and blood-filled lymphatics in the developing omentum. Altogether, these results highlight a novel context for epigenetically regulated crosstalk between macrophages, blood vessels, and lymphatics.

Progesterone Receptor Modulates Extraembryonic Mesoderm and Cardiac Progenitor Specification during Mouse Gastrulation.

Progesterone treatment is commonly employed to promote and support pregnancy. While maternal tissues are the main progesterone targets in humans and mice, its receptor (PGR) is expressed in the murine embryo, questioning its function during embryonic development. Progesterone has been previously associated with murine blastocyst development. Whether it contributes to lineage specification is largely unknown. Gastrulation initiates lineage specification and generation of the progenitors contributing to all organs. Cells passing through the primitive streak (PS) will give rise to the mesoderm and endoderm. Cells emerging posteriorly will form the extraembryonic mesodermal tissues supporting embryonic growth. Cells arising anteriorly will contribute to the embryonic heart in two sets of distinct progenitors, first (FHF) and second heart field (SHF). We found that PGR is expressed in a posterior-anterior gradient in the PS of gastrulating embryos. We established in vitro differentiation systems inducing posterior (extraembryonic) and anterior (cardiac) mesoderm to unravel PGR function. We discovered that PGR specifically modulates extraembryonic and cardiac mesoderm. Overexpression experiments revealed that PGR safeguards cardiac differentiation, blocking premature SHF progenitor specification and sustaining the FHF progenitor pool. This role of PGR in heart development indicates that progesterone administration should be closely monitored in potential early-pregnancy patients undergoing infertility treatment.

Evolution of reproductive strategies in the species-rich land snail subfamily Phaedusinae (Stylommatophora: Clausiliidae).

Most of the present knowledge on animal reproductive mode evolution, and possible factors driving transitions between oviparity and viviparity is based on studies on vertebrates. The species rich door snail (Clausiliidae) subfamily Phaedusinae represents a suitable and unique model for further examining parity evolution, as three different strategies, oviparity, viviparity, and the intermediate mode of embryo-retention, occur in this group. The present study reconstructs the evolution of reproductive strategies in Phaedusinae based on time-calibrated molecular phylogenetics, reproductive mode examinations and ancestral state reconstruction. Our phylogenetic analysis employing multiple mitochondrial and nuclear markers identified a well-supported clade (including the tribes Phaedusini and Serrulinini) that contains species exhibiting various reproductive strategies. This clade evolved from an oviparous most recent common ancestor according to our reconstruction. All non-oviparous taxa are confined to a highly supported subclade, coinciding with the tribe Phaedusini. Both oviparity and viviparity occur frequently in different lineages of this subclade that are not closely related. During Phaedusini diversification, multiple transitions in reproductive strategy must have taken place, which could have been promoted by a high fitness of embryo-retaining species. The evolutionary success of this group might result from the maintenance of various strategies.

Comparison of intravascular access methods applied by nurses wearing personal protective equipment in simulated COVID-19 resuscitation: A randomized crossover simulation trial.

BACKGROUND: Prehospital emergency care of children is challenging. In the era of the COVID-19 pandemic, when medical personnel should use personal protective equipment against aerosol-generating procedures, the efficiency of medical procedures may decrease. The study objective was to evaluate the effectiveness of different intravascular access methods applied by nurses wearing biosafety Level-2 suits in simulated paediatric COVID-19 resuscitation. METHODS: A prospective, randomized, crossover, single-blinded simulation trial was performed. Nursing staff attending Advanced Cardiovascular Life Support courses accredited by the American Heart Association participated in the study. A total of 65 nurses were recruited and randomly assigned to different study groups. They received standard training on intravascular access methods employing distinct devices. The participants wore biosafety Level-2 suits and performed vascular access with the following intraosseous devices: NIO-P, EZ-IO, and Jamshidi needle; intravenous (IV) access was used as a reference method. Both the order of participants and the access methods were random. Each participant performed intravascular access with each of the four methods tested. The effectiveness of the first attempt to obtain intravascular access and the following time parameters were analysed: the time between grasping the intravascular device out of the original packing until infusion line connection. The ease of the procedure was measured with a visual analogue scale (1 - easy; 10 - difficult). RESULTS: The first attempt success rate of intravascular access by using NIO-P and EZ-IO equalled 100% and was statistically significantly higher than that with the Jamshidi needle (80.0%; p = 0.02) and with the IV method (69.2%; p = 0.005). The time required to connect the infusion line varied and amounted to 33 ± 4 s for NIO-P compared to 37 ± 6.7 s for EZ-IO (p<0.001), 43 ± 7 s for Jamshidi (p<0.001), and 98.5 ± 10 s for IV access (p<0.001). The procedure was easiest in the case of NIO-P and EZ-IO (2 ± 1 points; p=1.0) compared with Jamshidi (5 ± 3 points; p<0.001) and IV access (7 ± 2 points; p<0.001). CONCLUSION: The study provides evidence that nurses wearing biosafety Level-2 suits were able to obtain intraosseous access faster and more effectively as compared with IV access during simulated COVID-19 paediatric resuscitation. The most effective method of intravascular access was the NIO-P intraosseous device. Further clinical trials are necessary to confirm the results.

Phylogeography of freshwater planorbid snails reveals diversification patterns in Eurasian continental islands.

BACKGROUND: Islands have traditionally been the centre of evolutionary biological research, but the dynamics of immigration and differentiation at continental islands have not been well studied. Therefore, we focused on the Japanese archipelago, the continental islands located at the eastern end of the Eurasian continent. While the Japanese archipelago is characterised by high biodiversity and rich freshwater habitats, the origin and formation mechanisms of its freshwater organisms are not clear. In order to clarify the history of the planorbid gastropod fauna, we conducted phylogenetic analysis, divergence time estimation, ancestral state reconstruction, and lineage diversity estimations. RESULTS: Our analyses revealed the formation process of the planorbid fauna in the Japanese archipelago. Most lineages in the Japanese archipelago have closely related lineages on the continent, and the divergence within the Japanese lineages presumably occurred after the late Pliocene. In addition, each lineage is characterised by different phylogeographical patterns, suggesting that immigration routes from the continent to the Japanese archipelago differ among lineages. Furthermore, a regional lineage diversity plot showed that the present diversity in the Japanese archipelago potentially reflects the differentiation of lineages within the islands after the development of the Japanese archipelago. CONCLUSIONS: Although additional taxon sampling and genetic analysis focused on each lineage are needed, our results suggest that immigration from multiple routes just prior to the development of the Japanese archipelago and subsequent diversification within the islands are major causes of the present-day diversity of the Japanese planorbid fauna.

Directed differentiation of human iPSC into insulin producing cells is improved by induced expression of PDX1 and NKX6.1 factors in IPC progenitors.

BACKGROUND: Induced pluripotent stem cells (iPSC) possess an enormous potential as both, scientific and therapeutic tools. Their application in the regenerative medicine provides new treatment opportunities for numerous diseases, including type 1 diabetes. In this work we aimed to derive insulin producing cells (IPC) from iPS cells established in defined conditions. METHODS: We optimized iPSC generation protocol and created pluripotent cell lines with stably integrated PDX1 and NKX6.1 transgenes under the transcriptional control of doxycycline-inducible promoter. These cells were differentiated using small chemical molecules and recombinant Activin A in the sequential process through the definitive endoderm, pancreatic progenitor cells and insulin producing cells. Efficiency of the procedure was assessed by quantitative gene expression measurements, immunocytochemical stainings and functional assays for insulin secretion. RESULTS: Generated cells displayed molecular markers characteristic for respective steps of the differentiation. The obtained IPC secreted insulin and produced C-peptide with significantly higher hormone release level in case of the combined expression of PDX1 and NKX6.1 induced at the last stage of the differentiation. CONCLUSIONS: Efficiency of differentiation of iPSC to IPC can be increased by concurrent expression of PDX1 and NKX6.1 during progenitor cells maturation. Protocols established in our study allow for iPSC generation and derivation of IPC in chemically defined conditions free from animal-derived components, which is of the utmost importance in the light of their prospective applications in the field of regenerative medicine.

Filling the gaps in ecology of tropical tiger beetles (Coleoptera: Cicindelidae): first quantitative data of sexual dimorphism in semi-arboreal Therates from the Philippine biodiversity hotspot.

Background: Sexual dimorphism, driven by sexual selection, leads to varied morphological distinctions in male and female insects, providing insights into selection pressures across species. However, research on the morphometric variability within specific taxa of tiger beetles (Coleoptera: Cicindelidae), particularly arboreal and semi-arboreal species, remains very limited. Methods: We investigate sexual dimorphism in six semi-arboreal Therates tiger beetle taxa from the Philippines, focusing on morphological traits. We employed morphometric measurements and multivariate analyses to reveal patterns of sexual dimorphism between sexes within the taxa. Results: Our results indicate significant sexual dimorphism in elytra width, with females consistently displaying broader elytra, potentially enhancing fecundity. Notable sexual size dimorphism was observed in Therates fulvipennis bidentatus and T. coracinus coracinus, suggesting heightened sexual selection pressures on male body size. Ecological factors, mating behavior, and female mate choice might contribute to the observed morphological variation. These findings emphasize the need for further studies to comprehend mating dynamics, mate choice, and ecological influences on morphological variations in semi-arboreal and arboreal tiger beetles.

Rapid detection of anti-Vaccinia virus neutralizing antibodies.

Increasing infections with Monkeypox and Cowpox viruses pose a continuous and growing threat to human health. The standard method for detecting poxvirus neutralizing antibodies is the plaque-reduction neutralization test that is specific but also time-consuming and laborious. Therefore, a rapid and reliable method was developed to determine neutralizing antibody titers within twelve hours. The new assay measures viral mRNA transcription as a marker for actively replicating virus after incomplete neutralization using real-time PCR.

Intraosseous vascular access in emergency and trauma settings: a comparison of the most universally used intraosseous devices.

Introduction: Obtaining successful vascular access is an essential component of the emergency and trauma setting. The modern practice of medicine advocates IO access for patients in a critical condition, especially when IV access is problematic or unobtainable. Various medical devices allowing for IO access have been coined and used in the management of critical patients.Areas covered: This study aims to review the literature regarding different intraosseous devices used to obtain vascular access (Bone Injection Gun (BIG), EZ-IO, NIO, Jamshidi, and First Access for Shock and Trauma (FAST-1) and discuss their clinical and experimental role in the emergency and trauma settings.Expert opinion: The development of medical technology contributes to an increasing number of intraosseous devices facilitating vascular access in challenging scenarios, including cardiopulmonary resuscitation, anaphylactic, or hypovolemic shock. Each of these devices provides an effective route for fluid resuscitation, drug delivery, laboratory evaluation, and shortening the timeframe for established vascular access, provided that the person obtaining the access is acquainted with the use of the device.

Correlation between takotsubo cardiomyopathy and SARS-CoV-2 infection.

Takotsubo cardiomyopathy (TTS), known as stress cardiomyopathy, is a rare disorder characterized by acute and transient left ventricular systolic and diastolic dysfunction, often associated with a stressful, emotional or physical event. TTS may be closely related to SARS-CoV-2 infection and the ongoing pandemic. The enormous emotional stress caused by the pandemic and respiratory infections caused by SARS-CoV-2 could be potential triggers for TTS. The case series cited above implicates that TTS should be considered in the differential diagnosis across the entire spectrum of myocardial injury in SARS-CoV-2 infected patients. Myocardial damage associated with SARS-CoV-2 infection is usually attributed to sepsis, hypoxemia, coronary artery disease, and myocarditis. We hypothesize that TTS may also play a role among these lesions.

A TALE/HOX code unlocks WNT signalling response towards paraxial mesoderm.

One fundamental yet unresolved question in biology remains how cells interpret the same signalling cues in a context-dependent manner resulting in lineage specification. A key step for decoding signalling cues is the establishment of a permissive chromatin environment at lineage-specific genes triggering transcriptional responses to inductive signals. For instance, bipotent neuromesodermal progenitors (NMPs) are equipped with a WNT-decoding module, which relies on TCFs/LEF activity to sustain both NMP expansion and paraxial mesoderm differentiation. However, how WNT signalling activates lineage specific genes in a temporal manner remains unclear. Here, we demonstrate that paraxial mesoderm induction relies on the TALE/HOX combinatorial activity that simultaneously represses NMP genes and activates the differentiation program. We identify the BRACHYURY-TALE/HOX code that destabilizes the nucleosomes at WNT-responsive regions and establishes the permissive chromatin landscape for de novo recruitment of the WNT-effector LEF1, unlocking the WNT-mediated transcriptional program that drives NMPs towards the paraxial mesodermal fate.

Intraosseous versus intravenous access while wearing personal protective equipment: a meta-analysis in the era of COVID-19.

BACKGROUND: Obtaining vascular access is one of the key procedures performed in patients in emergency settings. AIMS: The study was conducted as a meta­analysis and a systematic review and aimed to address the following question: which intravascular access method should be used in patients with COVID­19 when wearing full personal protective equipment (PPE)? METHODS: We performed a systematic search of PubMed, EMBASE, and CENTRAL databases for randomized controlled trials that compared intravascular access methods used by operators wearing full level C PPE. We evaluated procedure duration and the success rate of intraosseous and peripheral intravenous accesses. RESULTS: Eight randomized controlled trials were included in quantitative synthesis. The use of PPE during intravascular access procedures had an impact on procedure duration in the case of intraosseous access (mean difference [MD], 11.69; 95% CI, 6.47-16.92; P <0.001), as well as reduced the success rate of intraosseous access by 0.8% and intravenous access by 10.1%. Under PPE conditions, intraosseous access, compared with peripheral intravenous access, offered a shorter procedure time (MD, -41.43; 95% CI, -62.36 to -24.47; P <0.001). CONCLUSION: This comprehensive meta­analysis suggested that the use of PPE significantly extends the duration of intravascular procedures. However, under PPE conditions, operators were able to obtain intraosseous access in a shorter time and with a higher success rate than in the case of intravenous access.

Anthropogenic transformations of river ecosystems are not always bad for the environment: Multi-taxa analyses of changes in aquatic and terrestrial environments after dredging of a small lowland river.

Rivers are one of the most commonly transformed aquatic ecosystems. Most papers present significantly negative effects of activities such as dredging or channel regulation on the ecological status of rivers. The purpose of this work was to compare the response of various groups of invertebrates (Mollusca, Hydrachnidia, Odonata, Heteroptera, Coleoptera and Trichoptera) to an intervention involving dredging in conjunction with the removal of riparian vegetation. Habitat diversity increased after the dredging, and more individuals and species were caught than before the dredging. The increase in habitat diversity after the dredging translated into an increase in the species diversity of most investigated groups. Individual groups of invertebrates showed varied responses to the dredging, depending on the role of the terrestrial phase in their life cycle: the greater the role of the terrestrial phase in the life cycle, the more the group was affected by changes in the terrestrial environment following the intervention. In consequence, the intervention had the greatest negative impact on insects, and among these, on adult Odonata. The following conclusions can be drawn: (1) Dredging can benefit a previously anthropogenically transformed river ecosystem by increasing habitat diversity; (2) Odonata are particularly useful for assessing the impact of this type of intervention on invertebrate communities. They can be considered good indicators of habitat disturbances in both aquatic and terrestrial ecosystems.