Locally Preferred Structure and Frustration in Glassforming Liquids: A Clue to Polyamorphism?

We propose that the concept of liquids characterized by a given locally preferred structure (LPS) could help in understanding the observed phenomenon of polyamorphism. ``True polyamorphism'' would involve the competition between two (or more) distinct LPS, one favored at low pressure because of its low energy and one favored at high pressure because of its small specific volume, as in tetrahedrally coordinated systems. ``Apparent polyamorphism'' could be associated with the existence of a poorly crystallized defect-ordered phase with a large unit cell and small crystallites, which may be illustrated by the metastable glacial phase of the fragile glassformer triphenylphosphite; the apparent polyamorphism might result from structural frustration, i. e., a competition between the tendency to extend the LPS and a global constraint that prevents tiling of the whole space by the LPS.Comment: 11, 6 figures, Proceedings of the Conference "Horizons in Complex Systems", Messina; in honor of the 60th birthday of H.E. Stanle

Whole-genome sequencing reveals widespread presence of Staphylococcus capitis NRCS-A clone in neonatal units across the United Kingdom

OBJECTIVE: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK. METHODS: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms. RESULTS: We analysed WGS data of 838S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005-2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer. CONCLUSIONS: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection

The detection, survival and persistence of Staphylococcus capitis NRCS-A in neonatal units in England

BACKGROUND: The multi-drug resistant Staphylococcus capitis clone, NRCS-A is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. AIM: To investigate the potential for S. capitis to colonise surfaces within NICUs. METHODS: Surface swabs were collected from four NICUs with and without known NRCS-A colonisations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. FINDINGS: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whilst S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for 3 days with minimal losses in viability (< 0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. CONCLUSION: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment

How old are you now? A new ageing method for nonadults based on dental wear

The main aim of this study is to present a novel method of nonadult (ca. 1–19 years) age‐at‐death estimation using the dental wear of deciduous, mixed deciduous‐permanent, and permanent dentitions, including the incisors, canines, premolars, and first and second molars. The stage‐based method is derived from degrees of dental wear in known‐age (n = 39) and estimated‐age (n = 11) nonadults containing 951 teeth from the predominately 19th century cemetery of Middenbeemster, The Netherlands. The need for such a method is warranted in cases where dental development and/or eruption cannot be assessed for age‐at‐death estimation. As well, by establishing a baseline for normal age‐related nonadult tooth wear, users may better document wear that could be due to extramasticatory behaviours. The regression analysis reveals a strong quadratic correlation—F(2, 47) = 555.1, p R2 = .95, standard error of the estimate = 1.14, residual sum of squares (RSS) = 68.89, predicted residual error sum of squares (PRESS) = 77.67—between age and wear and multivariate adaptive regression splines (R2 = .95, generalised cross validation = 1.67, RSS = 67.68, PRESS = 89.34), which are used to develop an R‐package that users may employ to estimate age‐at‐death from dental wear. The accuracy of this method (78–98%) is evaluated using leave‐one‐out cross‐validation. Analyses of males versus females, deciduous versus permanent, upper versus lower, and anterior versus posterior teeth revealed no apparent reason to warrant separate methods for these groups of separated dentitions. This method fills a disciplinary gap in the understudied area of deciduous and nonadult dental wear and hopes to stimulate much future research. With the R‐package, we also provide the foundation and framework for the development of additional reference populations across different spatiotemporal contexts, to make the method more widely applicable. Bioarchaeolog

Solution Behavior and Activity of a Halophilic Esterase under High Salt Concentration

Background: Halophiles are extremophiles that thrive in environments with very high concentrations of salt. Although the salt reliance and physiology of these extremophiles have been widely investigated, the molecular working mechanisms of their enzymes under salty conditions have been little explored. Methodology/Principal Findings: A halophilic esterolytic enzyme LipC derived from archeaon Haloarcula marismortui was overexpressed from Escherichia coli BL21. The purified enzyme showed a range of hydrolytic activity towards the substrates of p-nitrophenyl esters with different alkyl chains (n = 2−16), with the highest activity being observed for p-nitrophenyl acetate, consistent with the basic character of an esterase. The optimal esterase activities were found to be at pH 9.5 and [NaCl] = 3.4 M or [KCl] = 3.0 M and at around 45°C. Interestingly, the hydrolysis activity showed a clear reversibility against changes in salt concentration. At the ambient temperature of 22°C, enzyme systems working under the optimal salt concentrations were very stable against time. Increase in temperature increased the activity but reduced its stability. Circular dichroism (CD), dynamic light scattering (DLS) and small angle neutron scattering (SANS) were deployed to determine the physical states of LipC in solution. As the salt concentration increased, DLS revealed substantial increase in aggregate sizes, but CD measurements revealed the maximal retention of the α-helical structure at the salt concentration matching the optimal activity. These observations were supported by SANS analysis that revealed the highest proportion of unimers and dimers around the optimal salt concentration, although the coexistent larger aggregates showed a trend of increasing size with salt concentration, consistent with the DLS data. Conclusions/Significance: The solution α-helical structure and activity relation also matched the highest proportion of enzyme unimers and dimers. Given that all the solutions studied were structurally inhomogeneous, it is important for future work to understand how the LipC's solution aggregation affected its activity

Inflammatory Transcriptome Profiling of Human Monocytes Exposed Acutely to Cigarette Smoke

<div><h3>Background</h3><p>Cigarette smoking is responsible for 5 million deaths worldwide each year, and is a major risk factor for cardiovascular and lung diseases. Cigarette smoke contains a complex mixture of over 4000 chemicals containing 10¹⁵ free radicals. Studies show smoke is perceived by cells as an inflammatory and xenobiotic stimulus, which activates an immune response. The specific cellular mechanisms driving cigarette smoke-induced inflammation and disease are not fully understood, although the innate immune system is involved in the pathology of smoking related diseases.</p> <h3>Methodology/Principle findings</h3><p>To address the impact of smoke as an inflammagen on the innate immune system, THP-1 cells and Human PBMCs were stimulated with 3 and 10% (v/v) cigarette smoke extract (CSE) for 8 and 24 hours. Total RNA was extracted and the transcriptome analysed using Illumina BeadChip arrays. In THP-1 cells, 10% CSE resulted in 80 genes being upregulated and 37 downregulated by ≥1.5 fold after 8 hours. In PBMCs stimulated with 10% CSE for 8 hours, 199 genes were upregulated and 206 genes downregulated by ≥1.5 fold. After 24 hours, the number of genes activated and repressed by ≥1.5 fold had risen to 311 and 306 respectively. The major pathways that were altered are associated with cell survival, such as inducible antioxidants, protein chaperone and folding proteins, and the ubiquitin/proteosome pathway.</p> <h3>Conclusions</h3><p>Our results suggest that cigarette smoke causes inflammation and has detrimental effects on the metabolism and function of innate immune cells. In addition, THP-1 cells provide a genetically stable alternative to primary cells for the study of the effects of cigarette smoke on human monocytes.</p> </div

Comparison of diagnoses of early-onset sepsis associated with use of Sepsis Risk Calculator versus NICE CG149: a prospective, population-wide cohort study in London, UK, 2020-2021.

OBJECTIVE: We sought to compare the incidence of early-onset sepsis (EOS) in infants ≥34 weeks' gestation identified >24 hours after birth, in hospitals using the Kaiser Permanente Sepsis Risk Calculator (SRC) with hospitals using the National Institute for Health and Care Excellence (NICE) guidance. DESIGN AND SETTING: Prospective observational population-wide cohort study involving all 26 hospitals with neonatal units colocated with maternity services across London (10 using SRC, 16 using NICE). PARTICIPANTS: All live births ≥34 weeks' gestation between September 2020 and August 2021. OUTCOME MEASURES: EOS was defined as isolation of a bacterial pathogen in the blood or cerebrospinal fluid (CSF) culture from birth to 7 days of age. We evaluated the incidence of EOS identified by culture obtained >24 hours to 7 days after birth. We also evaluated the rate empiric antibiotics were commenced >24 hours to 7 days after birth, for a duration of ≥5 days, with negative blood or CSF cultures. RESULTS: Of 99 683 live births, 42 952 (43%) were born in SRC hospitals and 56 731 (57%) in NICE hospitals. The overall incidence of EOS (24 hours was 2.3/100 000 (n=1) for SRC vs 7.1/100 000 (n=4) for NICE (OR 0.5, 95% CI (0.1 to 2.7)). This corresponded to (1/20) 5% (SRC) vs (4/45) 8.9% (NICE) of EOS cases (χ=0.3, p=0.59). Empiric antibiotics were commenced >24 hours to 7 days after birth in 4.4/1000 (n=187) for SRC vs 2.9/1000 (n=158) for NICE (OR 1.5, 95% CI (1.2 to 1.9)). 3111 (7%) infants received antibiotics in the first 24 hours in SRC hospitals vs 8428 (15%) in NICE hospitals. CONCLUSION: There was no significant difference in the incidence of EOS identified >24 hours after birth between SRC and NICE hospitals. SRC use was associated with 50% fewer infants receiving antibiotics in the first 24 hours of life