Atropine sulfate as a continuous intravenous infusion for the treatment of organophosphate toxicity in a cat.

Case summary: A 1-year-old male neutered domestic shorthair cat presented on an emergency basis with clinical signs suspected to be secondary to organophosphate (OP) toxicity. The control of clinical abnormalities (bradycardia, obtundation, tachypnea, anorexia) was achieved using high-dose continuous rate intravenous infusion (CRI) of atropine sulfate (maximum rate 0.1 mg/kg/h). After 5 days of hospitalization, the patient made a full clinical recovery without the development of atropine toxicity, intermediate syndrome or delayed polyneuropathy at 4 weeks after discharge. Relevance and novel information: Treatment of OP toxicity in cats is sparsely reported in veterinary literature. Current standards of treatment and published protocols recommend the use of atropine sulfate as intermittent boluses for the treatment of muscarinic signs of toxicity; however, there is a paucity of information regarding the safety and efficacy of atropine sulfate as a CRI for severe toxicosis as described in humans. This report includes the first published case using such a treatment protocol in a cat.

Healthcare professionals' perspectives on use of PCSK9 inhibitors in cardiovascular disease: an in-depth qualitative study.

AIM: Injectable medicines such as PCSK-9 inhibitors are increasingly used to manage risk factors for cardiovascular events with little information around the perceptions of healthcare professionals (HCPs) on the administrative and clinical practicalities. The aim was to identify the facilitators and barriers on the use of injectable therapies with CV benefits through interviews with HCPs. METHODS AND RESULTS: Qualitative interviews were conducted in the United Kingdom (London and Leeds) and Italy (Rome and Milan) in 2021. Coding was undertaken using NVivo and thematic analysis performed. A total of 38 HCPs were interviewed, 19 in each country composing of physicians (n = 18), pharmacists (n = 10), nurses (n = 9) and pharmacy technician (n = 1). Four themes emerged: (i) Clinicians' previous experiences with injectable therapies (ii) Challenges with patients' behaviours and beliefs (iii) Clinicians' knowledge of injectable therapies and therapeutic inertia and (iv) Organisational and governance issues. The behaviour and beliefs from healthcare professionals focused on facilitating behaviour change as well as the poor interdisciplinary working and collaboration. Therapeutic inertia was raised where physicians either lacked awareness of injectable therapies or were unwilling to prescribe them. The importance of facilitating patient education on injection techniques was highlighted while organisational and governance issues identified the lack of guidance to inform practice. Clear pathways are required to identify those who were eligible for injectable therapies as well as on how injectables should be prescribed. CONCLUSION: If medicine optimisation is to be achieved, there needs to be structured processes in place to identify eligible patients and the development of educational material.

The Influence of the 1988 and 2003 IOM Future of Public Health Reports on the CDC.

The landmark 1988 Institute of Medicine report The Future of Public Health served the public health community well by pointing to what needed to be done, fostering a sense of urgency, and offering concrete directions to be pursued. In this article, the impact of the 1988 report, and of the subsequent 2003 report on the Centers for Disease Control and Prevention (CDC), is considered by tracing the course of the ideas that influenced the consciousness of the public health community and subsequently catalyzed concrete action. Among these ideas was that "public health is in disarray." This assessment led to an awareness that something needed to be done. Further, by stating that the public health enterprise had 3 core functions (assessment, policy development, and assurance), the 1988 report set in motion policy development to address the "disarray." At a more fundamental level, both reports championed the need for governmental public health (particularly at the CDC) to take action to strengthen the capacity of local and state public health agencies to address a growing range of public health threats and emergencies. (Am J Public Health. 2024;114(5):489-494. https://doi.org/10.2105/AJPH.2024.307598).

Poetry in motion: catching molecules in action.

Researchers have long sought to `see' proteins and other macromolecules in motion, to better understand their functions. Technological developments, notably advances in serial crystallography, are now making these dreams a reality, heralding a new era of kinetic crystallography.

Blunt mechanism chest wall injury: initial patient assessment and acute care priorities.

Blunt mechanism chest wall injury (CWI) is commonly seen in the emergency department (ED), since it is present in around 15% of trauma patients. The thoracic cage protects the heart, lungs and trachea, thereby supporting respiration and circulation, so injury to the thorax can induce potentially life-threatening complications. Systematic care pathways have been shown to improve outcomes for patients presenting with blunt mechanism CWI, but care is not consistent across the UK. Emergency nurses have a crucial role in assessing and treating patients who present to the ED with blunt mechanism CWI. This article discusses the initial assessment and acute care priorities for this patient group. It also presents a prognostic model for predicting the probability of in-hospital complications following blunt mechanism CWI.

Properties of Layered TMDC Superlattices for Electrodes in Li-Ion and Mg-Ion Batteries.

In this work, we present a first-principles investigation of the properties of superlattices made from transition metal dichalcogenides for use as electrodes in lithium-ion and magnesium-ion batteries. From a study of 50 pairings, we show that, in general, the volumetric expansion, intercalation voltages, and thermodynamic stability of vdW superlattice structures can be well approximated with the average value of the equivalent property for the component layers. We also found that the band gap can be reduced, improving the conductivity. Thus, we conclude that superlattice construction can be used to improve material properties through the tuning of intercalation voltages toward specific values and by increasing the stability of conversion-susceptible materials. For example, we demonstrate how pairing SnS2 with systems such as MoS2 can change it from a conversion to an intercalation material, thus opening it up for use in intercalation electrodes.

Poly-γ-glutamylation of biomolecules.

Poly-γ-glutamate tails are a distinctive feature of archaeal, bacterial, and eukaryotic cofactors, including the folates and F420. Despite decades of research, key mechanistic questions remain as to how enzymes successively add glutamates to poly-γ-glutamate chains while maintaining cofactor specificity. Here, we show how poly-γ-glutamylation of folate and F420 by folylpolyglutamate synthases and γ-glutamyl ligases, non-homologous enzymes, occurs via processive addition of L-glutamate onto growing γ-glutamyl chain termini. We further reveal structural snapshots of the archaeal γ-glutamyl ligase (CofE) in action, crucially including a bulged-chain product that shows how the cofactor is retained while successive glutamates are added to the chain terminus. This bulging substrate model of processive poly-γ-glutamylation by terminal extension is arguably ubiquitous in such biopolymerisation reactions, including addition to folates, and demonstrates convergent evolution in diverse species from archaea to humans.

Computational Study of the Enhancement of Graphene Electrodes for Use in Li-Ion Batteries via Forming Superlattices with Transition Metal Dichalcogenides.

In our study, we examined nine transition metal dichalcogenide (TMDC)-graphene superlattices as potential Li-ion intercalation electrodes. We determined their voltages, with ScS2-graphene in T- and R-phases showing the highest at around 3 V, while the others ranged from 0 to 1.5 V. Most superlattices exhibited minimal volumetric expansion (5 to 10%), similar to NMC (8%), except for SnS2-T and NiS2-T, which expanded up to nearly 20%. We evaluated their capacities using a stability metric, EIS, and found that ScS2-T, ScS2-R, and TiS2-T could be intercalated up to two Li ions per MX2 unit without decomposing to Li2S, yielding capacities of 306.77 mA h/g for both ScS2 phases and 310.84 mA h/g for TiS2-T, roughly equivalent to LiC2. MoS2-T could accept Li up to a limit of a = 15/16 in LiaMoS2Cb, corresponding to a capacity of 121.29 mA h/g (equivalent to LiC4). Examining the influence of graphene layers on MoS2-T, we observed a voltage decrease and an initial EIS decrease before effectively flat lining, which is due to charge donation to the middle graphene layer, reducing the electron concentration near the TMDC layer. As graphene layers increased, overall volume expansion decreased with Li intercalation, which is attributed to the in-plane expansion changing. Our results underscore the potential of TMDC-graphene superlattices as Li-ion intercalation electrodes, offering low volumetric expansions, high capacities, and a wide voltage range. These superlattices all show an increase in the capacity of the graphene.

Building consensus on the selection criteria used when providing regional anaesthesia for rib fractures. An e-Delphi study amongst a UK-wide expert panel.

BACKGROUND: Rib fractures are associated with significant morbidity and mortality, and providing adequate analgesia is paramount in preventing early complications from these injuries. Multiple regional anaesthetic techniques can be used to provide analgesia for these injuries; however, few evidence-based guidelines exist for their use. The aim of this study was to establish consensus within an expert group on the selection criteria used when choosing regional anaesthetic techniques for rib fractures. METHODS: The Delphi technique is a mixed-methods study format which uses a longitudinal survey process to develop consensus opinion amongst an expert group. A three-round modified e-Delphi study was undertaken using an online survey platform. Round one established cohort characteristics and identified key factors considered important by the group when selecting regional anaesthetic techniques for rib fractures. Subsequent rounds used Likert scales and free text comments to rate the participants' level of agreement with various statements generated from the first-round responses. The final consensus threshold was established as at least 70% of respondents stating, 'Strongly Disagree' or 'Disagree' or alternatively 'Agree' or 'Strongly Agree'. RESULTS: An expert panel of UK-based consultants in anaesthesia and/or intensive care medicine was recruited. Participants worked in a variety of tertiary- and non-tertiary trauma care settings and were varied in their years of experience, approximate annual rib fracture caseload and preference for various anaesthetic techniques in rib fracture management. 54 participants took part in round one and generated 60 statements which were further analysed in an iterative process involving a total of three rounds. A total of 28 statements ultimately reached the pre-defined threshold for consensus within the expert group. CONCLUSIONS: This e-Delphi study succeeded in building consensus across multiple statements relating to the selection criteria for regional anaesthesia in patients with rib fractures. These consensus statements can inform clinical practice, guide future research priorities and can be integrated into decision-making pathways across multiple hospital settings.

Exploring perceptions of digital technology and digital skills among newly registered nurses and clinical managers.

BACKGROUND: Digital technology has an increasing role in healthcare, but staff lack opportunities to develop their digital skills and there is a lack of research on education and training in digital technology for staff. AIM: To explore nurses' perceptions of the use of digital technology in their practice and to identify the digital skills required by newly registered nurses to work in a digitally enabled environment. METHOD: Individual semi-structured interviews were conducted on an online communication platform with nine participants - four newly registered nurses and five senior nurses working in clinical and/or management roles. Inductive thematic analysis was used to analyse the data. FINDINGS: Several barriers and facilitators to the use of digital technology were identified, including around infrastructure, time, skills, training, support, leadership, familiarity and confidence. The use of digital technology may enhance care consistency and increase patient autonomy, but it may also erode nurse-patient relationships. CONCLUSION: Digital technology can enhance patient care but organisational barriers, notably in relation to digital literacy training, need to be addressed for nurses to fully adopt it.

Domain structure and cross-linking in a giant adhesin from the Mobiluncus mulieris bacterium.

Cell-surface proteins known as adhesins enable bacteria to colonize particular environments, and in Gram-positive bacteria often contain autocatalytically formed covalent intramolecular cross-links. While investigating the prevalence of such cross-links, a remarkable example was discovered in Mobiluncus mulieris, a pathogen associated with bacterial vaginosis. This organism encodes a putative adhesin of 7651 residues. Crystallography and mass spectrometry of two selected domains, and AlphaFold structure prediction of the remainder of the protein, were used to show that this adhesin belongs to the family of thioester, isopeptide and ester-bond-containing proteins (TIE proteins). It has an N-terminal domain homologous to thioester adhesion domains, followed by 51 immunoglobulin (Ig)-like domains containing ester- or isopeptide-bond cross-links. The energetic cost to the M. mulieris bacterium in retaining such a large adhesin as a single gene or protein construct suggests a critical role in pathogenicity and/or persistence.

Queues, crowds, and angry mobs: Face identification under distraction in a virtual airport.

In visual environments, selective attention must be employed to focus on task-relevant stimuli. A key question here concerns the extent to which other stimuli within the visual field influence target processing. In this study, we ask whether face identity matching is subject to similar effects from irrelevant stimuli in the visual field, specifically task-irrelevant people. Although most previous studies rely on highly controlled face and body stimuli presented in isolation, here we use a more realistic environment. Participants take the role of passport officers and must match a person's face to their photo-ID, while other people appear in the background, waiting to be processed. Presenting an interactive virtual environment on screen (Experiments 1 and 2) or in immersive VR (Experiment 3), we generally found no evidence for distraction from background people on face-matching accuracy. However, when immersed in VR, an angry crowd in the background delayed matching speed while not affecting accuracy. We discuss the theoretical implications of these results and their potential importance in practical settings.

Individual-based analyses reveal effects of behavioral and demographic variables associated with multi-annual reproductive success of male and female lake sturgeon.

Quantifying effects of individual attributes and population demographic characteristics that affect inter- and intrasexual interactions and adult reproductive success, and the spatial and temporal contexts in which they are expressed is important to effective species management. Multi-year individual-based analyses using genetically determined parentage allowed the examination of variables associated with the reproductive success of male and female lake sturgeon (Acipenser fulvescens) in the well-studied population in Black Lake, Michigan, USA. Spawning lake sturgeon (a total of 599 individuals where many were captured more than once based on 1024 total captures) and larvae (N = 3436) were genotyped during each of seven consecutive years (2001-2007). Factors associated with individual reproductive success differed between sexes and varied among spawning groups within a year and among years depending on spawning date (higher reproductive success earlier in the season for females) and spawning locations (higher reproductive success in upstream spawning zones for females). Female reproductive success increased nonlinearly with increasing body size. Male reproductive success increased with increasing residence time in spawning areas and, to a modest degree, with increasing body size in a nonlinear fashion. Fixed effects of repeatability in spawn timing and location across years led to consistently higher or lower reproductive success for females. Results identified factors, including time spent at spawning areas by males and intersexual encounters and mate number, that contributed to higher interindividual variance in reproductive success and affected population levels of recruitment, the degree of subpopulation genetic structure (lack of isolation by time), and effective population size.

Behavioral evidence of olfactory imprinting during embryonic and larval stages in lake sturgeon.

Many migratory fishes are thought to navigate to natal streams using olfactory cues learned during early life stages. However, direct evidence for early-life olfactory imprinting is largely limited to Pacific salmon, and other species suspected to imprint show life history traits and reproductive strategies that raise uncertainty about the generality of the salmonid-based conceptual model of olfactory imprinting in fishes. Here, we studied early-life olfactory imprinting in lake sturgeon (Acipenser fulvescens), which have a life cycle notably different from Pacific salmon, but are nonetheless hypothesized to home via similar mechanisms. We tested one critical prediction of the hypothesis that early-life olfactory imprinting guides natal homing in lake sturgeon: that exposure to odorants during early-life stages results in increased activity when exposed to those odorants later in life. Lake sturgeon were exposed to artificial odorants (phenethyl alcohol and morpholine) during specific developmental windows and durations (limited to the egg, free-embryo, exogenous feeding larvae and juvenile stages), and later tested as juveniles for behavioral responses to the odorants that were demonstrative of olfactory memory. Experiments revealed that lake sturgeon reared in stream water mixed with artificial odorants for as little as 7 days responded to the odorants in behavioral assays over 50 days after the initial exposure, specifically implicating the free-embryo and larval stages as critical imprinting periods. Our study provides evidence for olfactory imprinting in a non-salmonid fish species, and supports further consideration of conservation tactics such as stream-side rearing facilities that are designed to encourage olfactory imprinting to targeted streams during early life stages. Continued research on lake sturgeon can contribute to a model of olfactory imprinting that is more generalizable across diverse fish species and will inform conservation actions for one of the world's most imperiled fish taxonomic groups.

Patients' perceptions on the facilitators and barriers using injectable therapies in dyslipidaemia: An empirical qualitative descriptive international study.

BACKGROUND: Injectable medicines are increasingly used to manage abnormal levels of lipids, which is a major risk factor for cardiovascular events. Enhancing our understanding of patients' perceptions of these injectables, can inform practice with the aim of increasing uptake and medication adherence. AIM: To explore patient's experiences of using injectables and to identify potential facilitators and barriers to using injectable therapies in dyslipidaemia. DESIGN: A qualitative descriptive study using semi-structured interviews was conducted with patients who were using injectables to manage their cardiovascular conditions. METHODS: A total of 56 patients, 30 from the United Kingdom and 26 from Italy, were interviewed online from November 2020 to June 2021. Interviews were transcribed and schematic content analysis performed. RESULTS: Four distinct themes emerged from interviews with patients and caregivers: (i) Their behaviours and personal beliefs; (ii) Knowledge and education about injectable medication; (iii) Clinical skills and previous experiences and (iv) Organizational and governance. Participants expressed initial fears such as needle phobia, and their concerns about commencing therapy were compounded by a lack of accessible information. However, patients' pre-existing knowledge of lipid lowering medication, previous experience with statins and history of adverse side effects informed their decision-making regarding using injectables. Organization and governance-related issues were primarily around the distribution and management of medication supply within primary care, and the lack of a standardized clinical support monitoring system. CONCLUSION: Changes are needed in clinical practice to better educate and support patients to improve the uptake of injectables and optimize their use of these medications in the management of dyslipidaemia. IMPACT: This study suggests that injectable therapies were acceptable to people with cardiovascular disease. However, healthcare professionals need to play a key role in improving education and providing support to aid patients' decision-making regarding commencing and adhering to injectable therapies. REPORTING METHOD: The study adhered to the Consolidated Criteria for Reporting Qualitative Research. PATIENT OR PUBLIC CONTRIBUTION: There was no patient or public contribution.

AlphaFold and the future of structural biology.

This editorial acknowledges the transformative impact of new machine-learning methods, such as the use of AlphaFold, but also makes the case for the continuing need for experimental structural biology.

AlphaFold and the future of structural biology.

This editorial acknowledges the transformative impact of new machine-learning methods, such as the use of AlphaFold, but also makes the case for the continuing need for experimental structural biology.