A ROTEM hypocoagulable profile at admission seems promising for the early detection of sepsis in neonates while the degree of hypocoagulation may be associated with sepsis severity. What is Known: • The early phase of septicemia might be difficult to be recognized in neonates. In adult septic patients, the diagnostic and prognostic role of thromboelastometry (ROTEM) have been extensively investigated. • Limited data are available on the role of ROTEM as an indicator of early neonatal sepsis. What is New: • ROTEM measurements indicate an early appearance of hypocoagulability in neonatal sepsis, while the degree of hypocoagulation might be associated with severity of sepsis. • ROTEM could be a useful tool in the early detection of sepsis in neonates.

Background and aimsUnderstanding the structures and functions of carbon-based molecules in soils is an important goal in the context of soils as an ecosystem function of immense importance. Polysaccharides are implicated in maintaining soil aggregate status but have not been extensively dissected in terms of their structures and soil adhesion properties. This is largely because of the technical difficulties in identifying polysaccharide structures and quantifying any functional properties.MethodsHere, we describe the use of a novel nitrocellulose-based adhesion assay to determine the relative capacities for soil adhesion of over twenty plant and microbial polysaccharides that are likely to be present in soil and to contribute to organic matter content and properties. Weights of soil adhered to spots of known amounts of specific polysaccharides were quantified by scanning of the nitrocellulose sheets.ResultsThe most effective polysaccharides identified from this survey included chitosan, β-1,3-glucan, gum tragacanth, xanthan and xyloglucan. We also demonstrate that the soil adhesion assay is suitable to assess the soil-binding properties of plant exudates.ConclusionsThe soil adhesion assay will be useful for the functional dissection of the organic matter components of soils and also of the factors involved in soil attachment to plant roots and in rhizosheath formation.

Background: Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Treatment options include biologics and tofacitinib. Objectives: We aim to summarize the evidence on efficacy and safety of biologics and tofacitinib in moderate-to-severe UC. Methods: PubMed, Embase, Scopus, and the Cochrane Library were systematically searched to identify meta-analyses of randomized controlled trials assessing adalimumab, golimumab, infliximab, vedolizumab, and tofacitinib in UC. Efficacy outcomes included induction and maintenance of clinical response, clinical remission and mucosal healing. Safety outcomes included adverse events and serious adverse events. Results: The overview involved 31 meta-analyses. All four biologics and tofacitinib were superior to placebo regarding efficacy. Indirect comparisons suggested that infliximab may be better than adalimumab and golimumab to induce clinical response and mucosal healing. Safety analyses indicated no increased rates of adverse events, except for infliximab. Conclusions: Biologics and tofacitinib are efficacious and safe for treating UC. These findings can support clinical decisionmaking.

Evaluating causal effects in the presence of interference is challenging in network-based studies of hard to reach populations. Like many such populations, people who inject drugs (PWID) are embedded in social networks and often exert influence on others in their network. In our setting, the study design is observational with a non-randomized network-based HIV prevention intervention. The information is available on each participant and their connections that confer possible shared HIV risk behaviors through injection and sexual risk behaviors. We consider two inverse probability weighted (IPW) estimators to quantify the population-level effects of non-randomized interventions on subsequent health outcomes. We demonstrated that these two IPW estimators are consistent, asymptotically normal, and derived a closed form estimator for the asymptotic variance, while allowing for overlapping interference sets (groups of individuals in which the interference is assumed possible). A simulation study was conducted to evaluate the finite-sample performance of the estimators. We analyzed data from the Transmission Reduction Intervention Project, which ascertained a network of PWID and their contacts in Athens, Greece, from 2013 to 2015. We evaluated the effects of community alerts on HIV risk behavior in this observed network, where the links between participants were defined by using substances or having unprotected sex together. In the study, community alerts were distributed to inform people of recent HIV infections among individuals in close proximity in the observed network. The estimates of the risk differences for both IPW estimators demonstrated a protective effect. The results suggest that HIV risk behavior can be mitigated by exposure to a community alert when an increased risk of HIV is detected in the network.

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Our aim is to determine the most appropriate laboratory tests, besides anti-factor Xa (anti-FXa) chromogenic assays, to estimate the degree of anticoagulation with apixaban and compare it with that of rivaroxaban in real-world patients. Twenty patients with nonvalvular atrial fibrillation treated with apixaban 5 mg twice daily and 20 patients on rivaroxaban 20 mg once daily were studied. Conventional coagulation tests, thrombin generation assay (TGA), and thromboelastometry (nonactivated TEM [NATEM] assay) were performed in the 40 patients and 20 controls. The anti-FXa chromogenic assays were used to measure apixaban and rivaroxaban plasma levels. The NATEM measurements showed no significant difference between the 2 groups of patients. Concerning TGA, endogenous thrombin potential (ETP) was significantly decreased in patients on rivaroxaban as compared to those treated with apixaban ( P < .003). A statistically significant, strong inverse correlation between apixaban plasma concentrations and ETP ( P < .001) was observed. Apixaban significantly reduces ETP compared to controls, but to a lesser extent than rivaroxaban. Thrombin generation assay might provide additional information on apixaban exposure, which is required in order to individualize treatment especially for patients with a high bleeding risk. Our findings have to be further investigated in studies with larger sample sizes, in the entire range of apixaban exposure, with other direct oral anticoagulants, and in relation to clinical outcomes.

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic diseases characterised by dental enamel malformation. Pathogenic variants in at least 33 genes cause syndromic or non-syndromic AI. Recently variants in RELT, encoding an orphan receptor in the tumour necrosis factor (TNF) superfamily, were found to cause recessive AI, as part of a syndrome encompassing small stature and severe childhood infections. Here we describe four additional families with autosomal recessive hypomineralised AI due to previously unreported homozygous mutations in RELT. Three families carried a homozygous missense variant in the fourth exon (c.164C>T, p.(T55I)) and a fourth family carried a homozygous missense variant in the 11th exon (c.1264C>T, p.(R422W)). We found no evidence of additional syndromic symptoms in affected individuals. Analyses of tooth microstructure with computerised tomography and scanning electron microscopy suggest a role for RELT in ameloblasts' coordination and interaction with the enamel matrix.Microsatellite genotyping in families segregating the T55I variant reveals a shared founder haplotype. These findings extend the RELT pathogenic variant spectrum, reveal a founder mutation in the UK Pakistani population and provide detailed analysis of human teeth affected by this hypomineralised phenotype, but do not support a possible syndromic presentation in all those with RELT-variant associated AI. K E Y W O R D S amelogenesis imperfecta, enamel, RELT, tumour necrosis factor receptor

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