Genomic epidemiology and longitudinal sampling of ward wastewater environments and patients reveals complexity of the transmission dynamics of bla KPC -carbapenemase-producing Enterobacterales in a hospital setting

Background: Healthcare-associated wastewater and asymptomatic patient reservoirs colonized by carbapenemase-producing Enterobacterales (CPE) contribute to nosocomial CPE dissemination, but the characteristics and dynamics of this remain unclear. Methods: We systematically sampled wastewater sites (n = 4488 samples; 349 sites) and patients (n = 1247) across six wards over 6–12 months to understand blaKPC-associated CPE (KPC-E) diversity within these reservoirs and transmission in a healthcare setting. Up to five KPC-E-positive isolates per sample were sequenced (Illumina). Recombination-adjusted phylogenies were used to define genetically related strains; assembly and mapping-based approaches were used to characterize antimicrobial resistance genes, insertion sequences (ISs) and Tn4401 types/target site sequences. The accessory genome was evaluated in some of the largest clusters, and those crossing reservoirs. Results: Wastewater site KPC-E-positivity was substantial [101/349 sites (28.9%); 228/5601 (4.1%) patients cultured]. Thirteen KPC-E species and 109 strains were identified using genomics, and 24% of wastewater and 26% of patient KPC-E-positive samples harboured one or more strains. Most diversity was explained by the individual niche, suggesting localized factors are important in selection and spread. Tn4401 + flanking target site sequence diversity was greater in wastewater sites (P < 0.001), which might favour Tn4401-associated transposition/evolution. Shower/bath- and sluice/mop-associated sites were more likely to be KPC-E-positive (adjusted OR = 2.69; 95% CI: 1.44–5.01; P = 0.0019; and adjusted OR = 2.60; 95% CI: 1.04–6.52; P = 0.0410, respectively). Different strains had different blaKPC dissemination dynamics. Conclusions: We identified substantial and diverse KPC-E colonization of wastewater sites and patients in this hospital setting. Reservoir and niche-specific factors (e.g. microbial interactions, selection pressures), and different strains and mobile genetic elements likely affect transmission dynamics. This should be considered in surveillance and control strategies

Social cohesion among healthcare workers during COVID-19: qualitative research in Indonesia, Nepal, and Vietnam

Existing literature has portrayed numerous challenges that healthcare workers (HCWs) faced during the COVID-19 pandemic, such as heightened risks of transmission against the scarcity of protective equipment, burgeoning workload, and emotional distress, to name a few. However, most studies explored HCWs' experiences at the individual level rather than examining the collective responses. Exploring these experiences could reveal the social-cultural locality of the pandemic while identifying the system constraints in public health emergencies. As part of a mixed-method study on COVID-19 pandemic impacts, we analysed qualitative interview data with 129 HCWs and health-related staff to explore their experiences during the pandemic between 2020 and 2021 in Vietnam, Indonesia, and Nepal. Using Bahers' sociological framework, Community of Fate, we describe five themes reflecting the formation of a community of HCWs and the social cohesion underlying their efforts to survive hardship. The first three themes characterise the HCW community of fate, including (1) Recognition of extreme work-related danger, (2) physical and figurative closures where HCWs restrict themselves from the outside world, (3) chronic ordeals with overwhelming workload and responsibilities, encompassing recurrent mental health challenges. Against such extreme hardship, cohesive bonding and social resilience are reflected through two additional themes: (4) a mutual sense of moral and professional duty to protect communities, (5) the vertical and horizontal convergence among HCWs across levels and among government departments. We discuss these HCWs’ challenges in relation to systemic vulnerabilities while advocating for increasing investment in public health and collaboration across government sectors to prepare for emergency situation

The many faces of natural theology: diverse projects, distinct roles, and the pursuit of clarity

The term ‘natural theology’ provokes a variety of reactions, spanning from whole-hearted endorsement to passionate rejection. Charged as it is with polemical and pejorative undertones, this debate begs for an intervention. If the scholarly community is to engage constructively with the concept and practice of natural theology – either by way of acceptance, rejection, or something in between – clarity in its definition and identification is imperative. The aim of this paper is to try to shed some light on three of the most common definitions of ‘natural theology’ in contemporary scholarship, to provide clarity about the ways in which they differ, and to propose some conceptual refinements in the hope that, if adopted, more fruitful discourse may take place in relation to this much-debated and interdisciplinary phrase

Transit time flow measurement in arterial grafts

Coronary artery bypass grafting (CABG) is one of the foundations of treatment for coronary artery disease. While it has improved substantially since its inception more than 50 years ago, including a rising use of multiple arterial grafting, intraoperative quality assessment is yet to be disseminated as an integral part of the procedure. Herein we review the fundamentals of intraoperative quality assessment in CABG using transient time flow measurement (TTFM) with a focus on its use in arterial grafting

Stress-shape misalignment in confluent cell layers

In tissue formation and repair, the epithelium undergoes complex patterns of motion driven by the active forces produced by each cell. Although the principles governing how the forces evolve in time are not yet clear, it is often assumed that the contractile stresses within the cell layer align with the axis defined by the body of each cell. Here, we simultaneously measured the orientations of the cell shape and the cell-generated contractile stresses, observing correlated, dynamic domains in which the stresses were systematically misaligned with the cell body. We developed a continuum model that decouples the orientations of contractile stress and cell body. The model recovered the spatial and temporal dynamics of the regions of misalignment in the experiments. These findings reveal that the cell controls its contractile forces independently from its shape, suggesting that the physical rules relating cell forces and cell shape are more flexible than previously thought

Molecular sequence analysis of Crimean-Congo haemorrhagic fever virus and the discovery and characterisation of novel sarbecoviruses

Zoonotic diseases and viral infections impose substantial health and economic challenges globally. Timely prediction, detection, and response to these threats are paramount for zoonoses prevention. Recent strides in next-generation sequencing and computational capabilities have elevated pathogen genomics to its application as a leading method for predication, and both real-time and retrospective tracking of zoonotic infections. Globally, there are a limited number of facilities which can routinely process and characterise hazard group 4 agents which cause high consequence viral infections. Many HG4 agents are underrepresented by genomic sequences in the public domain which prevents accurate prediction of risk regions and dissemination. Crimean-Congo haemorrhagic fever virus is a globally distributed virus with limited genomic representation compared to other forms of evidence, serological or molecular. This project characterised novel genomes from archival and contemporary clinical samples stored at Porton Down. We characterise the heterogeneous viral population circulating in Turkey in 2015 and corroborate current predictions for the global dissemination and divergence of CCHFv with its origin in Southern Africa. The COVID-19 pandemic provided a unique opportunity for the characterisation of sarbecoviruses from horseshoe bats in the UK. Prior to 2020, surveillance in horseshoe bats had been focused on populations in China and Hong Kong leaving a largely undefined western limit for sarbecoviruses within horseshoe bat populations. Here we detect and characterise the first Sarbecovirus from lesser horseshoe bats in Europe and the first in horseshoe bats in the UK. Additionally, continued longitudinal surveillance highlighted an accelerated evolutionary rate within the receptor binding motif, potentially highlighting it as a zoonotic risk

Changes in Oxidised Phospholipids in Response to Oxidative Stress in Microtubule-Associated Protein Tau ( MAPT ) Mutant Dopamine Neurons

Microtubule-associated protein Tau (MAPT) is strongly associated with the development of neurodegenerative diseases. In addition to driving the formation of neurofibrillary tangles (NFT), mutations in the MAPT gene can also cause oxidative stress through hyperpolarisation of the mitochondria. This study explores the impact that MAPT mutation is having on phospholipid metabolism in iPSC-derived dopamine neurons, and to determine if these effects are exacerbated by mitochondrial and endoplasmic reticulum stress. Neurons that possessed a mutated copy of MAPT were shown to have significantly higher levels of oxo-phospholipids (Oxo-PL) than wild-type neurons. Oxidation of the hydrophobic fatty acid side chains changes the chemistry of the phospholipid leading to disruption of membrane function and potential cell lysis. In wild-type neurons, both mitochondrial and endoplasmic reticulum stress increased Oxo-PL abundance; however, in MAPT mutant neurons mitochondrial stress appeared to have a minimal effect. Endoplasmic reticulum stress, surprisingly, reduced the abundance of Oxo-PL in MAPT mutant dopamine neurons, and we postulate that this reduction could be modulated through hyperactivation of the unfolded protein response and X-box binding protein 1. Overall, the results of this study contribute to furthering our understanding of the regulation and impact of oxidative stress in Parkinson’s disease pathology

Observation of the B c + → J / ψ π + π 0 decay

The first observation of the Bc+→J/ψπ+π0 decay is reported with high significance using proton-proton collision data, corresponding to an integrated luminosity of 9 fb−1, collected with the LHCb detector at centre-of-mass energies of 7, 8, and 13 TeV. The ratio of its branching fraction relative to the Bc+→J/ψπ+ channel is measured to beBBc+→J/ψπ+π0BBc+→J/ψπ+=2.80±0.15±0.11±0.16, where the first uncertainty is statistical, the second systematic and the third related to imprecise knowledge of the branching fractions for B+ → J/ψK*+ and Bc+→J/ψπ+ decays, which are used to determine the π0 detection efficiency. The π+π0 mass spectrum is found to be consistent with the dominance of an intermediate ρ+ contribution in accordance with a model based on QCD factorisation