Antifungal stewardship in the UK: where are we now?

Background: Antifungal stewardship (AFS) is the judicious use of today's antifungal agents with the aim of improving patient outcomes and preserving their future effectiveness. Antifungal resistance (AFR) is increasing globally, with more patients at risk of Invasive Fungal Disease (IFD), highlighting the urgent need to standardize AFS practices in the UK. The aim of this position paper is to understand the current AFS landscape in the UK.

Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma.

Two APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires grainyhead-like transcription factor 3 (GRHL3).

Adopting prospective antimicrobial stewardship (AMS) practice in high-risk immunosuppressed groups: an urgent call to action in the era of antimicrobial resistance (AMR).

Life-saving immunosuppressive treatments including intensive chemotherapy and bone marrow transplantation expose patients to a considerable risk of death from infection globally. With evolving AMR and transmission, this could spell disaster for patients across the world and society at large. Antimicrobial stewardship (AMS) and prompt appropriate management of potentially fatal, emergent infections are essential.

Specifying how intervention content is communicated: Development of a Style of Delivery Ontology.

Investigating and enhancing the effectiveness of behaviour change interventions requires detailed and consistent specification of all aspects of interventions. We need to understand not only their content, that is the specific techniques, but also the source, mode, schedule, and style in which this content is delivered. Delivery style refers to the manner by which content is communicated to intervention participants.

Differentiation signals induce expression via GRHL3 in squamous epithelia and squamous cell carcinoma.

Two APOBEC (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-like) DNA cytosine deaminase enzymes (APOBEC3A and APOBEC3B) generate somatic mutations in cancer, driving tumour development and drug resistance. Here we used single cell RNA sequencing to study and expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas is expressed in keratinocytes entering mitosis, we show that expression is confined largely to terminally differentiating cells and requires Grainyhead-like transcription factor 3 (GRHL3).

An ontology of mechanisms of action in behaviour change interventions.

Background: Behaviour change interventions influence behaviour through causal processes called "mechanisms of action" (MoAs). Reports of such interventions and their evaluations often use inconsistent or ambiguous terminology, creating problems for searching, evidence synthesis and theory development. This inconsistency includes the reporting of MoAs.

Representation of adults with class III obesity in studies assessing validity of self-reported energy intake using doubly labeled water: A systematic review.

The measurement of habitual energy intake remains a challenge in nutrition research. High levels of misreporting, particularly among adults with obesity, have been observed when comparing self-reported energy intake to energy expenditure assessed via the doubly labeled water technique. Little is known about misreporting in adults with class III obesity (body mass index ≥40 kg/m).

The Impact of Weight Bias and Stigma on the 24 h Dietary Recall Process in Adults with Overweight and Obesity: A Pilot Study.

People with overweight and obesity tend to both underreport dietary energy intake and experience weight stigma. This exploratory pilot study aimed to determine the relationship between weight bias and weight stigma and energy intake reporting accuracy. Thirty-nine weight-stable adults with BMI ≥ 25 completed three 24 h dietary recalls; indirect calorimetry to measure resting metabolic rate; a survey measuring weight stigma, psychosocial constructs, and physical activity; and a semi-structured qualitative interview.

Building Leadership Through Partnerships: Using Concept Mapping to Develop Community Capacity to Address Gender-Based Violence.

Background: To address an unmet need for community-driven gender-based violence (GBV) responses in areas with high levels of precarious employment, a community-based organization partnered with academic researchers and community members to use concept mapping to inform the design of a leadership development program.

Objectives: The objectives of the research were to identify and prioritize the skills, knowledge, and resources that "worker-leaders" (informal activists) need to help prevent and reduce acts of GBV directed toward individuals working in low-wage and precarious employment situations.

Methods: Using concept mapping as part of a community-based participatory project, the community-academic research team elicited input from Latinx and Korean residents from low-income immigrant communities.

Remote constraint induced therapy of the upper extremity (ReCITE): A feasibility study protocol.

Background: Difficulty using the upper extremity in everyday activities is common after stroke. Constraint-induced movement therapy (CIMT) has been shown to be effective in both sub-acute and chronic phases of stroke recovery and is recommended in clinical practice guidelines for stroke internationally. Despite reports of equivalence of outcome when stroke rehabilitation interventions are delivered using telehealth, there has been limited evaluation of CIMT when using this mode of delivery.

Impaired inhibitory processing: a new therapeutic target for autism and psychosis?

In the healthy brain, homeostatic balance between excitation and inhibition maintains neural stability. Reduced inhibition may explain shared symptoms observed in autism and psychosis. Here we review evidence suggesting that altered levels of gamma-aminobutyric acid (GABA) may underlie both disorders, providing a potential cross-diagnostic therapeutic target.

Substitution of warthog NF-κB motifs into RELA of domestic pigs is not sufficient to confer resilience to African swine fever virus.

African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe. Unlike domestic pigs, warthogs, which are wildlife hosts of the virus, do not succumb to the lethal effects of infection. There are three amino acid differences between the sequence of the warthog and domestic pig RELA protein; a subunit of the NF-κB transcription factor that plays a key role in regulating the immune response to infections.

Image-Based Dietary Assessment Ability of Dietetics Students and Interns.

Image-based dietary assessment (IBDA) may improve the accuracy of dietary assessments, but no formalized training currently exists for skills relating to IBDA. This study investigated nutrition and dietetics students' and interns' IBDA abilities, the training and experience factors that may contribute to food identification and quantification accuracy, and the perceived challenges to performing IBDA. An online survey containing images of known foods and serving sizes representing common American foods was used to assess the ability to identify foods and serving sizes.

Comparison of Mediterranean Pteropod Shell Biometrics and Ultrastructure from Historical (1910 and 1921) and Present Day (2012) Samples Provides Baseline for Monitoring Effects of Global Change.

Anthropogenic carbon perturbation has caused decreases in seawater pH and increases in global temperatures since the start of the 20th century. The subsequent lowering of the saturation state of CaCO3 may make the secretion of skeletons more problematic for marine calcifiers. As organisms that precipitate thin aragonite shells, thecosome pteropods have been identified as being particularly vulnerable to climate change effects.

Near-future pH conditions severely impact calcification, metabolism and the nervous system in the pteropod Heliconoides inflatus.

Shelled pteropods play key roles in the global carbon cycle and food webs of various ecosystems. Their thin external shell is sensitive to small changes in pH, and shell dissolution has already been observed in areas where aragonite saturation state is ~1. A decline in pteropod abundance has the potential to disrupt trophic networks and directly impact commercial fisheries.

OCEANOGRAPHY. Contrasting futures for ocean and society from different anthropogenic CO₂ emissions scenarios.

The ocean moderates anthropogenic climate change at the cost of profound alterations of its physics, chemistry, ecology, and services. Here, we evaluate and compare the risks of impacts on marine and coastal ecosystems—and the goods and services they provide—for growing cumulative carbon emissions under two contrasting emissions scenarios. The current emissions trajectory would rapidly and significantly alter many ecosystems and the associated services on which humans heavily depend.

Selective diffusion barriers separate membrane compartments.

We have investigated exchange of molecules between different membrane domains on a highly compartmentalized cell, the spermatozoon. Using Alexa Fluor 555-cholera toxin B-subunit we have observed clustering of preexisting GM1 gangliosides which diffused across the anterior acrosome-equatorial segment interface but did not access the postacrosome. By contrast, single lipid and protein molecules readily exchanged between all three domains, although they diffused more slowly on nearing and crossing to the postacrosome.

Tracking diffusion of GM1 gangliosides and zona pellucida binding molecules in sperm plasma membranes following cholesterol efflux.

The molecules on mammalian spermatozoa that mediate recognition and binding to the zona pellucida of the egg are still not understood. Current concepts favour their assembly into multimolecular complexes in the plasma membrane in response to cholesterol efflux, an important step during sperm capacitation. Here, we track in real time diffusion of cross-linked clusters containing zona-binding molecules and GM1 gangliosides in the plasma membrane of live boar spermatozoa before and after cholesterol reduction.

The equatorial subsegment in mammalian spermatozoa is enriched in tyrosine phosphorylated proteins.

The equatorial subsegment (EqSS) was originally identified by atomic force microscopy as a discrete region within the equatorial segment of Artiodactyl spermatozoa. In this investigation, we show that the EqSS is enriched in tyrosine phosphorylated proteins and present preliminary evidence for its presence in mouse and rat spermatozoa. The anti-phosphotyrosine monoclonal antibody (McAb) 4G10 bound strongly and discretely to the EqSS of permeabilized boar, ram, and bull spermatozoa.

Binding of sperm proacrosin/beta-acrosin to zona pellucida glycoproteins is sulfate and stereodependent. Synthesis of a novel fertilization inhibitor.

Specific binding of spermatozoa to the zona pellucida that surrounds mammalian eggs is a key step in the fertilization process. However, the sperm proteins that recognise zona pellucida receptors remain contentious despite longstanding research efforts to identify them. Here we present evidence that proacrosin, a tissue-specific protein found within the acrosomal vesicle of all mammalian spermatozoa, is a multifunctional protein that mediates binding of acrosome-reacted spermatozoa to zona glycoproteins via a stereospecific polysulfate recognition mechanism.