Parameters for one health genomic surveillance of Escherichia coli from Australia.

Genomics is a cornerstone of modern pathogen epidemiology yet demonstrating transmission in a One Health context is challenging, as strains circulate and evolve within and between diverse hosts and environments. To identify phylogenetic linkages and better define relevant measures of genomic relatedness in a One Health context, we collated 5471 Escherichia coli genome sequences from Australia originating from humans (n = 2996), wild animals (n = 870), livestock (n = 649), companion animals (n = 375), environmental sources (n = 292) and food (n = 289) spanning over 36 years. Of the 827 multi-locus sequence types (STs) identified, 10 STs were commonly associated with cross-source genomic clusters, including the highly clonal ST131, pandemic zoonotic lineages such as ST95, and emerging human ExPEC ST1193.

Combined visualization of genomic and epidemiological data for outbreaks.

In epidemiological investigations, pathogen genomics can provide insights and test epidemiological hypotheses that would not have been possible through traditional epidemiology. Tools to synthesize genomic analysis with other types of data are a key requirement of genomic epidemiology. We propose a new 'phylepic' visualization that combines a phylogenomic tree with an epidemic curve.

The ester-containing prodrug NT-0796 enhances delivery of the NLRP3 inflammasome inhibitor NDT-19795 to monocytic cells expressing carboxylesterase-1.

NT-0796 is an ester prodrug which is metabolized by carboxylesterase-1 (CES1) to yield the carboxylic acid NDT-19795, an inhibitor of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome. When applied to human monocytes/macrophages which express CES1, however, NT-0796 is much more potent at inhibiting NLRP3 inflammasome activation than is NDT-19795. Comparison of the binding of NDT-19795 and NT-0796 in a cell-based NLRP3 target engagement assay confirms that NDT-19795 is the active species.

The Maintenance Model of Restrictive Practices: A Trauma-Informed, Integrated Model to Explain Repeated Use of Restrictive Practices in Mental Health Care Settings.

Nurses are at the forefront of care in mental health services but their role is conflicted; they carry the most responsibility for care and also for restrictive practices. The harmful effects of restrictive practices for mental health patients are well documented, have attracted negative media attention, public concern, and criticism directed specifically at nursing staff. The need to reduce restrictive practices has been highlighted by patients, carer groups, legislators, policy makers, academics, and mental health service providers.

Structured connectivity in the output of the cerebellar cortex.

The spatial organization of a neuronal circuit is critically important for its function since the location of neurons is often associated with function. In the cerebellum, the major output of the cerebellar cortex are synapses made from Purkinje cells onto neurons in the cerebellar nuclei, yet little has been known about the spatial organization of these synapses. We explored this question using whole-cell electrophysiology and optogenetics in acute sagittal cerebellar slices to produce spatial connectivity maps of cerebellar cortical output in mice.

Characterization of two affinity matured Anti-Yersinia pestis F1 human antibodies with medical countermeasure potential.

Yersinia pestis, the causative agent of plague and a biological threat agent, presents an urgent need for novel medical countermeasures due to documented cases of naturally acquired antibiotic resistance and potential person-to-person spread during a pneumonic infection. Immunotherapy has been proposed as a way to circumvent current and future antibiotic resistance. Here, we describe the development and characterization of two affinity matured human antibodies (αF1Ig AM2 and αF1Ig AM8) that promote survival of mice after exposure to aerosolized Y.

Nutrition-related predictors of complications and length of hospital stay following total pelvic exenteration surgery.

Background & Aims: Pelvic exenteration (PE) surgery is now a widely accepted procedure that is increasingly being performed worldwide but has significant morbidity. Although nutrition status, body mass index (BMI) and postoperative nutrition support practices are modifiable risk factors, few studies have examined the relationship of these with clinical outcomes following PE. The aim of this study was therefore to investigate the impact of these factors on postoperative complications and length of hospital stay (LOHS) following PE.

Readmission after discharge from a medium secure service between 1999 and 2017: A retrospective cohort study.

Background: Previous research into outcomes after treatment in medium secure psychiatric hospitals has mostly relied on pre-millennium data.

Aims: To examine patient and inpatient service-related factors associated with readmission within 2 years following discharge to the community or open conditions from conditions of medium security.

Methods: A retrospective cohort study of 137 patients discharged either to the community or to open conditions from one 64-bed South Wales Regional Medium Secure Hospital Unit between July 1999 and November 2017 was completed using data from healthcare records to document demographics, diagnosis and nature of index offences together with researcher-completed ratings of inpatient progress using the Dangerousness Understanding Recovery and Urgency Manual (DUNDRUM) Programme Completion and DUNDRUM Recovery scales.

Pharmacological Analysis of NLRP3 Inflammasome Inhibitor Sodium [(1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)carbamoyl][(1-methyl-1-pyrazol-4-yl)({[(2)-oxolan-2-yl]methyl})sulfamoyl]azanide in Cellular and Mouse Models of Inflammation Provides a Translational Framework.

Interleukin (IL)-1β is an apex proinflammatory cytokine produced in response to tissue injury and infection. The output of IL-1β from monocytes and macrophages is regulated not only by transcription and translation but also post-translationally. Release of the active cytokine requires activation of inflammasomes, which couple IL-1β post-translational proteolysis with pyroptosis.

Hippocampus, amygdala, and insula activation in response to romantic relationship dissolution stimuli: A case-case-control fMRI study on emerging adult students.

Background: Romantic relationship dissolutions (RRDs) are associated with posttraumatic stress symptoms (PTSS). Functional magnetic resonance imaging in RRD studies indicate overlapping neural activation similar to posttraumatic stress disorder. These studies combine real and hypothetical rejection, and lack contextual information and control and/or comparison groups exposed to non-RRD or DSM-5 defined traumatic events.

Snakebite envenoming: A systematic review and meta-analysis of global morbidity and mortality.

Background: Snakebite envenoming represents a significant and often neglected public health challenge, particularly in rural communities across tropical and subtropical regions. An estimated 1.2-5.

Grand challenges in entomology: Priorities for action in the coming decades.

Entomology is key to understanding terrestrial and freshwater ecosystems at a time of unprecedented anthropogenic environmental change and offers substantial untapped potential to benefit humanity in a variety of ways, from improving agricultural practices to managing vector-borne diseases and inspiring technological advances.We identified high priority challenges for entomology using an inclusive, open, and democratic four-stage prioritisation approach, conducted among the membership and affiliates (hereafter 'members') of the UK-based Royal Entomological Society (RES).A list of 710 challenges was gathered from 189 RES members.

Point-of-care ultrasound associated with shorter length of stay than computed tomography for renal colic.

Background: Despite similar diagnostic effectiveness for renal colic, computed tomography (CT) is more resource intensive than point-of-care ultrasound (PoCUS). We sought to compare Emergency Department (ED) length of stay (LOS) among patients with renal colic according to imaging modality utilized. We secondarily compared rates of infection, return ED visits, missed significant pathology, and urologic intervention.

Voxelotor improves red blood cell functionality in children with sickle cell anaemia: An ancillary study of the HOPE-KIDS 1 trial.

Introduction: Sickle haemoglobin (HbS) polymerisation perturbs red blood cell (RBC) rheology and drives sickle cell disease (SCD) pathophysiology. Voxelotor is an HbS polymerisation inhibitor that increases haemoglobin (Hb)-oxygen affinity.

Methods/results: In this 48-week, prospective, single-centre translational study, 10 children aged 4-11 years with SCD were treated with voxelotor.

Reversal of High Fat Diet-Induced Obesity, Systemic Inflammation, and Astrogliosis by the NLRP3 Inflammasome Inhibitors NT-0249 and NT-0796.

Systemic and cerebral inflammatory responses are implicated in the pathogenesis of obesity and associated metabolic impairment. While the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has been linked to obesity-associated inflammation, whether it contributes to the development or maintenance of obesity is unknown. We provide support for a direct role of saturated fatty acids, such as palmitic acid, as NLRP3 activating stimuli in obese states.

Analysis of SARS-CoV-2 antibody seroprevalence in Northern Ireland during 2020-2021.

Background: With the spread of SARS-CoV-2 impacting upon public health directly and socioeconomically, further information was required to inform policy decisions designed to limit virus spread during the pandemic. This study sought to contribute to serosurveillance work within Northern Ireland to track SARS-CoV-2 progression and guide health strategy.

Methods: Sera/plasma samples from clinical biochemistry laboratories were analysed for anti-SARS-CoV-2 antibodies.

Phalloplasty Flap Salvage Using a Superficial Circumflex Iliac Artery Perforator Propeller Flap.

Background: Partial phalloplasty flap loss presents an evolving challenge, largely due to the complex demands required for both aesthetics and function. We describe our novel experience using the superficial circumflex iliac perforator (SCIP) propeller flap for neophallus salvage when skin grafting alone provides insufficient soft tissue bulk or coverage.

Methods: We retrospectively reviewed patients who underwent SCIP propeller flap reconstruction after phalloplasty partial flap loss.

Mitochondrial damage and impaired mitophagy contribute to disease progression in SCA6.

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease that manifests in midlife and progressively worsens with age. SCA6 is rare, and many patients are not diagnosed until long after disease onset. Whether disease-causing cellular alterations differ at different disease stages is currently unknown, but it is important to answer this question in order to identify appropriate therapeutic targets across disease duration.

Target Cell Activation of a Structurally Novel NOD-Like Receptor Pyrin Domain-Containing Protein 3 Inhibitor NT-0796 Enhances Potency.

The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a central regulator of innate immunity, essential for processing and release of interleukin-1 and pyroptotic cell death. As endogenous NLRP3 activating triggers are hallmarks of many human chronic inflammatory diseases, inhibition of NLRP3 has emerged as a therapeutic target. Here we identify NDT-19795 as a novel carboxylic acid-containing NLRP3 activation inhibitor in both human and mouse monocytes and macrophages.

Enhancing Conductivity of Silver Nanowire Networks through Surface Engineering Using Bidentate Rigid Ligands.

Solution processable metallic nanomaterials present a convenient way to fabricate conductive structures, which are necessary in all electronic devices. However, they tend to require post-treatments to remove the bulky ligands around them to achieve high conductivity. In this work, we present a method to formulate a post-treatment free conductive silver nanowire ink by controlling the type of ligands around the silver nanowires.

Endosomal dysfunction contributes to cerebellar deficits in spinocerebellar ataxia type 6.

Spinocerebellar ataxia type 6 (SCA6) is a rare disease that is characterized by cerebellar dysfunction. Patients have progressive motor coordination impairment, and postmortem brain tissue reveals degeneration of cerebellar Purkinje cells and a reduced level of cerebellar brain-derived neurotrophic factor (BDNF). However, the pathophysiological changes underlying SCA6 are not fully understood.

INX-315, a Selective CDK2 Inhibitor, Induces Cell Cycle Arrest and Senescence in Solid Tumors.

Unlabelled: Cyclin-dependent kinase 2 (CDK2) is thought to play an important role in driving proliferation of certain cancers, including those harboring CCNE1 amplification and breast cancers that have acquired resistance to CDK4/6 inhibitors (CDK4/6i). The precise impact of pharmacologic inhibition of CDK2 is not known due to the lack of selective CDK2 inhibitors. Here we describe INX-315, a novel and potent CDK2 inhibitor with high selectivity over other CDK family members.

Sustainability of enhanced recovery after surgery programmes in gastrointestinal surgery: A scoping review.

Background: Enhanced Recovery After Surgery (ERAS) is an evidence-based intervention that is well-recognised across multiple surgical specialties as having potential to lead to improved patient and hospital outcomes. Little is known about sustainability of ERAS programmes.

Aims: This review aimed to describe available evidence evaluating sustainability of ERAS programmes in gastrointestinal surgery to understand: (a) how sustainability has been defined; (b) examine determinants of sustainability; (c) identify strategies used to facilitate sustainability; (d) identify adaptations to support sustainability; and (e) examine outcomes measured as indicators of sustainability of ERAS programmes.