Point‐of‐care lung ultrasound in patients with COVID‐19 – a narrative review

Ultrasound imaging of the lung and associated tissues may play an important role in the management of patients with COVID‐19–associated lung injury. Compared with other monitoring modalities, such as auscultation or radiographic imaging, we argue lung ultrasound has high diagnostic accuracy, is ergonomically favourable and has fewer infection control implications. By informing the initiation, escalation, titration and weaning of respiratory support, lung ultrasound can be integrated into COVID‐19 care pathways for patients with respiratory failure. Given the unprecedented pressure on healthcare services currently, supporting and educating clinicians is a key enabler of the wider implementation of lung ultrasound. This narrative review provides a summary of evidence and clinical guidance for the use and interpretation of lung ultrasound for patients with moderate, severe and critical COVID‐19–associated lung injury. Mechanisms by which the potential lung ultrasound workforce can be deployed are explored, including a pragmatic approach to training, governance, imaging, interpretation of images and implementation of lung ultrasound into routine clinical practice

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Feasibility study of hospital antimicrobial stewardship analytics using electronic health records

Background: Hospital antimicrobial stewardship (AMS) programmes are multidisciplinary initiatives to optimise the use of antimicrobials. Most hospitals depend on time-consuming manual audits to monitor clinicians’ prescribing. But much of the information needed could be sourced from electronic health records (EHRs). Objectives: To develop an informatics methodology to analyse characteristics of hospital AMS practice using routine electronic prescribing and laboratory records. Methods: Feasibility study using electronic prescribing, laboratory and clinical coding records from adult patients admitted to six specialties at Queen Elizabeth Hospital, Birmingham, UK (September 2017–August 2018). The study involved: (1) a review of antimicrobial stewardship standards of care; (2) their translation into concepts measurable from commonly available EHRs; (3) pilot application in an EHR cohort study (n=61,679 admissions). Results: We developed data modelling methods to characterise the use of antimicrobials (antimicrobial therapy episode linkage methods, therapy table, therapy changes). Prescriptions were linked into antimicrobial therapy episodes (mean 2.4 prescriptions/episode; mean length of therapy of 5.8 days) enabling production of several actionable findings. For example, 22% of therapy episodes for low-severity community acquired pneumonia were congruent with prescribing guidelines, with a tendency to use antibiotics with a broader spectrum. Analysis of therapy changes revealed a delay in switching from intravenous to oral therapy by an average 3.6 days [95% CI: 3.4; 3.7]. Performance of microbial cultures prior to treatment initiation occurred in just 22% of antibacterial prescriptions. The proposed methods enabled fine-grained monitoring of AMS practice all the way down to specialties, wards, and individual clinical teams by case mix, enabling more meaningful peer comparison. Conclusions: It is feasible to use hospital EHRs to construct rapid, meaningful measures of prescribing quality with potential to support quality improvement interventions (audit/feedback to prescribers), engagement with front-line clinicians on optimising prescribing, and AMS impact evaluation studies

Do Lions Panthera leo Actively Select Prey or Do Prey Preferences Simply Reflect Chance Responses via Evolutionary Adaptations to Optimal Foraging?

Research on coursing predators has revealed that actions throughout the predatory behavioral sequence (using encounter rate, hunting rate, and kill rate as proxy measures of decisions) drive observed prey preferences. We tested whether similar actions drive the observed prey preferences of a stalking predator, the African lion Panthera leo. We conducted two 96 hour, continuous follows of lions in Addo Elephant National Park seasonally from December 2003 until November 2005 (16 follows), and compared prey encounter rate with prey abundance, hunt rate with prey encounter rate, and kill rate with prey hunt rate for the major prey species in Addo using Jacobs' electivity index. We found that lions encountered preferred prey species far more frequently than expected based on their abundance, and they hunted these species more frequently than expected based on this higher encounter rate. Lions responded variably to non-preferred and avoided prey species throughout the predatory sequence, although they hunted avoided prey far less frequently than expected based on the number of encounters of them. We conclude that actions of lions throughout the predatory behavioural sequence, but particularly early on, drive the prey preferences that have been documented for this species. Once a hunt is initiated, evolutionary adaptations to the predator-prey interactions drive hunting success

Population structure and associated phenotypes of Salmonella enterica serovars Derby and Mbandaka overlap with host range

BACKGROUND:The Salmonella enterica serovar Derby is frequently isolated from pigs and turkeys whereas serovar Mbandaka is frequently isolated from cattle, chickens and animal feed in the UK. Through comparative genomics, phenomics and mutant construction we previously suggested possible mechanistic reasons why these serovars demonstrate apparently distinct host ranges. Here, we investigate the genetic and phenotypic diversity of these two serovars in the UK. We produce a phylogenetic reconstruction and perform several biochemical assays on isolates of S. Derby and S. Mbandaka acquired from sites across the UK between the years 2000 and 2010. RESULTS:We show that UK isolates of S. Mbandaka comprise of one clonal lineage which is adapted to proficient utilisation of metabolites found in soya beans under ambient conditions. We also show that this clonal lineage forms a biofilm at 25 °C, suggesting that this serovar maybe well adapted to survival ex vivo, growing in animal feed. Conversely, we show that S. Derby is made of two distinct lineages, L1 and L2. These lineages differ genotypically and phenotypically, being divided by the presence and absence of SPI-23 and the ability to more proficiently invade porcine jejunum derived cell line IPEC-J2. CONCLUSION:The results of this study lend support to the hypothesis that the differences in host ranges of S. Derby and S. Mbandaka are adaptations to pathogenesis, environmental persistence, as well as utilisation of metabolites abundant in their respective host environments

A review of camera trapping for conservation behaviour research

An understanding of animal behaviour is important if conservation initiatives are to be effective. However, quantifying the behaviour of wild animals presents significant challenges. Remote-sensing camera traps are becoming increasingly popular survey instruments that have been used to non-invasively study a variety of animal behaviours, yielding key insights into behavioural repertoires. They are well suited to ethological studies and provide considerable opportunities for generating conservation-relevant behavioural data if novel and robust methodological and analytical solutions can be developed. This paper reviews the current state of camera-trap-based ethological studies, describes new and emerging directions in camera-based conservation behaviour, and highlights a number of limitations and considerations of particular relevance for camera-based studies. Three promising areas of study are discussed: (1) documenting anthropogenic impacts on behaviour; (2) incorporating behavioural responses into management planning and (3) using behavioural indicators such as giving up densities and daily activity patterns. We emphasize the importance of reporting methodological details, utilizing emerging camera trap metadata standards and central data repositories for facilitating reproducibility, comparison and synthesis across studies. Behavioural studies using camera traps are in their infancy; the full potential of the technology is as yet unrealized. Researchers are encouraged to embrace conservation-driven hypotheses in order to meet future challenges and improve the efficacy of conservation and management processes

In situ characterization of advanced glycation end products (AGEs) in collagen and model extracellular matrix by solid state NMR

Non-enzymatic glycation of extracellular matrix with (U-13C5)-Dribose- 5-phosphate (R5P), enables in situ 2D ssNMR identification of many deleterious protein modifications and crosslinks, including previously unreported oxalamido and hemiaminal (CH3- CH(OH)NHR) substructures. Changes in charged residue proportions and distribution may be as important as crosslinking in provoking and understanding harmful tissue changes

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

Incidence, healthcare-seeking behaviours, antibiotic use and natural history of common infection syndromes in England: results from the Bug Watch community cohort study

Background: Better information on the typical course and management of acute common infections in the community could inform antibiotic stewardship campaigns. We aimed to investigate the incidence, management, and natural history of a range of infection syndromes (respiratory, gastrointestinal, mouth/dental, skin/soft tissue, urinary tract, and eye). Methods: Bug Watch was an online prospective community cohort study of the general population in England (2018–2019) with weekly symptom reporting for 6 months. We combined symptom reports into infection syndromes, calculated incidence rates, described the proportion leading to healthcare-seeking behaviours and antibiotic use, and estimated duration and severity. Results: The cohort comprised 873 individuals with 23,111 person-weeks follow-up. The mean age was 54 years and 528 (60%) were female. We identified 1422 infection syndromes, comprising 40,590 symptom reports. The incidence of respiratory tract infection syndromes was two per person year; for all other categories it was less than one. 194/1422 (14%) syndromes led to GP (or dentist) consultation and 136/1422 (10%) to antibiotic use. Symptoms usually resolved within a week and the third day was the most severe. Conclusions: Most people reported managing their symptoms without medical consultation. Interventions encouraging safe self-management across a range of acute infection syndromes could decrease pressure on primary healthcare services and support targets for reducing antibiotic prescribing