Antimicrobial Prescription Practices and Stewardship in Washington State Small and Mixed Animal Veterinary Medicine.

Introduction: Judicious antimicrobial use is essential for the continued treatment of infections in small and mixed animal veterinary medicine. To better support Washington (WA) State veterinarians in antimicrobial stewardship, we surveyed licensed small and mixed animal veterinarians and led group conversations regarding antimicrobial prescription practices.

Methods: Survey questions included demographic information, factors influencing prescription practices and clinical cases.

Regulation of the NLRP3 inflammasome by autophagy and mitophagy.

The NLRP3 inflammasome is a multiprotein complex that upon activation by the innate immune system drives a broad inflammatory response. The primary initial mediators of this response are pro-IL-1β and pro-IL-18, both of which are in an inactive form. Formation and activation of the NLRP3 inflammasome activates caspase-1, which cleaves pro-IL-1β and pro-IL-18 and triggers the formation of gasdermin D pores.

Gasdermin D and Gasdermin E Are Dispensable for Silica-Mediated IL-1β Secretion from Mouse Macrophages.

Silica crystals activate the NLRP3 inflammasome in macrophages, resulting in the caspase-1-dependent secretion of the proinflammatory cytokine IL-1β. Caspase-1-mediated cleavage of gasdermin D (GSDMD) triggers the formation of GSDMD pores, which drive pyroptotic cell death and facilitate the rapid release of IL-1β. However, the role of GSDMD in silica-induced lung injury is unclear.

Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia.

A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).

Dynamic reporters for probing real-time activation of human fibroblasts from single cells to populations.

Activation of fibroblasts is pivotal for wound healing; however, persistent activation leads to maladaptive processes and is a hallmark of fibrosis, where disease mechanisms are only partially understood. Human model systems complement animal models for both hypothesis testing and drug evaluation to improve the identification of therapeutics relevant to human disease. Despite advances, a challenge remains in understanding the dynamics of human fibroblast responses to complex microenvironment stimuli, motivating the need for more advanced tools to investigate fibrotic mechanisms.

Cell therapy biomanufacturing: integrating biomaterial and flow-based membrane technologies for production of engineered T-cells.

Adoptive T-cell therapies (ATCTs) are increasingly important for the treatment of cancer, where patient immune cells are engineered to target and eradicate diseased cells. The biomanufacturing of ATCTs involves a series of time-intensive, lab-scale steps, including isolation, activation, genetic modification, and expansion of a patient's T-cells prior to achieving a final product. Innovative modular technologies are needed to produce cell therapies at improved scale and enhanced efficacy.

Inflammasome-Independent Roles of NLR and ALR Family Members.

Pattern recognition receptors, including members of the NLR and ALR families, are essential for recognition of both pathogen- and host-derived danger signals. Several members of these families, including NLRP1, NLRP3, NLRC4, and AIM2, are capable of forming multiprotein complexes, called inflammasomes, that result in the activation of pro-inflammatory caspase-1. However, in addition to the formation of inflammasomes, a number of these family members exert inflammasome-independent functions.

SMART recovery for youth: a small, exploratory qualitative study examining the potential of a mutual-aid, peer support addictive behaviour change program for young people.

Background: SMART (Self-Management and Recovery Training) Recovery is a mutual-aid program informed by cognitive behaviour therapy and motivational interviewing that provides support for a range of addictive behaviours. SMART Recovery has not been adapted to target young people with addictive behaviours despite the potential to overcome important barriers affecting youth engagement in other addiction programs. This study aimed to engage young people and SMART Recovery facilitators in qualitative interviews and focus groups to explore the potential of such a program and gain specific insights for its development.

NLRP12-expressing dendritic cells mediate both dissemination of infection and adaptive immune responses in visceral leishmaniasis.

The NLR protein NLRP12 contributes to innate immunity, but the mechanism remains elusive. Infection of or wild-type mice with led to aberrant parasite tropism. Parasites replicated to higher levels in livers of mice than in the livers of WT mice and failed to disseminate to spleens.

Physical activity and screen time in Swedish children and adolescents: The generation pep study 2018-2021.

Aim: To analyse physical activity and screen time trends annually between 2018 and 2021 in large population-based samples of Swedish children and adolescents.

Methods: This is a repeated cross-sectional study using data collected over 4 years (2018-2021) using simple probability sampling of Swedish children and adolescents aged 4-17 years. The web-based questionnaire, including questions on physical activity and screen time, was filled out by a parent if the child was <12 years of age and by the adolescents themselves if they were ≥ 12 years.

Temporal analysis suggests a reciprocal relationship between 3D chromatin structure and transcription.

To infer potential causal relationships between 3D chromatin structure, enhancers, and gene transcription, we mapped each feature in a genome-wide fashion across eight narrowly spaced time points of macrophage activation. Enhancers and genes connected by loops exhibit stronger correlations between histone H3K27 acetylation and expression than can be explained by genomic distance or physical proximity alone. At these looped enhancer-promoter pairs, changes in acetylation at distal enhancers precede changes in gene expression.

The Pseudomonas aeruginosa Type III Secretion System Exoenzyme Effector ExoU Induces Mitochondrial Damage in a Murine Bone Marrow-Derived Macrophage Infection Model.

Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that causes nosocomial pneumonia, urinary tract infections, and bacteremia. A hallmark of P. aeruginosa pathogenesis is disruption of host cell function by the type III secretion system (T3SS) and its cognate exoenzyme effectors.

Tunable Blood Shunt for Neonates With Complex Congenital Heart Defects.

Despite advancements in procedures and patient care, mortality rates for neonatal recipients of the Norwood procedure, a palliation for single ventricle congenital malformations, remain high due to the use of a fixed-diameter blood shunt. In this study, a new geometrically tunable blood shunt was investigated to address limitations of the current treatment paradigm (e.g.

Incidence of interruptive penicillin allergy alerts in patients with previously documented beta-lactam exposure: Potential for leveraging the electronic health record to identify erroneous allergies.

Background: Approximately 10% of patients report allergies to penicillin, yet >90% of these allergies are not clinically significant. Patients reporting penicillin allergies are often treated with second-line, non-β-lactam antibiotics that are typically broader spectrum and more toxic. Orders for β-lactam antibiotics for these patients trigger interruptive alerts, even when there is electronic health record (EHR) data indicating prior β-lactam exposure.

Generation Pep Study: A population-based survey on diet and physical activity in 12,000 Swedish children and adolescents.

Aim: This study presents dietary intake and physical activity in a large nationally representative sample of children and adolescents in Sweden. It also reports the study protocol for the Generation Pep Study that will be used for yearly repeated measurements.

Methods: A random sample of children and adolescents aged 4-17 years living in Sweden was invited to fill in a Web-based questionnaire on dietary intake and physical activity.

Recruitment of pro-IL-1α to mitochondrial cardiolipin, via shared LC3 binding domain, inhibits mitophagy and drives maximal NLRP3 activation.

The balance between NLRP3 inflammasome activation and mitophagy is essential for homeostasis and cellular health, but this relationship remains poorly understood. Here we found that interleukin-1α (IL-1α)-deficient macrophages have reduced caspase-1 activity and diminished IL-1β release, concurrent with reduced mitochondrial damage, suggesting a role for IL-1α in regulating this balance. LPS priming of macrophages induced pro-IL-1α translocation to mitochondria, where it directly interacted with mitochondrial cardiolipin (CL).

Vesicular systems for dermal and transdermal drug delivery.

Dermal/transdermal drug delivery continues to grow in importance as a means of enhancing treatment activity while reducing toxicity by avoiding the systemic absorption of the drug. At the same time, this has led to the adjustment of a wide diversity of drug carriers. This paper begins with a review of the skin, including its structure and the parameters that influence drug diffusion, followed by strategies to improve dermal drug delivery.

Bridging 2D and 3D culture: probing impact of extracellular environment on fibroblast activation in layered hydrogels.

Many cell behaviors are significantly affected by cell culture geometry, though it remains unclear which geometry from two- to three-dimensional (2D to 3D) culture is appropriate for probing a specific cell function and mimicking native microenvironments. Toward addressing this, we established a 2.5D culture geometry, enabling initial cell spreading while reducing polarization to bridge between 2D and 3D geometries, and examined the responses of wound healing cells, human pulmonary fibroblasts, within it.

Tools for probing host-bacteria interactions in the gut microenvironment: From molecular to cellular levels.

Healthy function of the gut microenvironment is dependent on complex interactions between the bacteria of the microbiome, epithelial and immune (host) cells, and the surrounding tissue. Misregulation of these interactions is implicated in disease. A range of tools have been developed to study these interactions, from mechanistic studies to therapeutic evaluation.

Analysis of complex mixtures of polyglycerol fatty esters using liquid chromatography and high-resolution mass spectrometry: Retention, structural and relative composition study.

Polyglycerol esters (PGEs), produced by esterification of fatty acids on polyglycerols, were analysed by High Resolution Mass Spectrometry (HRMS), HPLC-MS and U-HPLC-MS. A structural study of PGEs in 4 samples synthesised by the Gattefossé company was carried out using an elemental analysis of HRMS spectra and modelling of all probable isomers and cyclic structures. The results were used to construct a structural database of all species present in the 4 samples.

In vitro and in vivo cardioprotective and metabolic efficacy of vitamin E TPGS/Apelin.

Aims: Apelin and vitamin E have been proposed as signaling molecules, but their synergistic role is unknown. The aim of this work was to develop vitamin E TPGS/Apelin system to test their cardioprotective and metabolic efficacy in vitro and in vivo.

Methods: FDA-approved surfactant D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-1000) and Apelin complex were characterized by physico-chemical methods (CMC determination, dynamic light scattering and circular dichroism).

Optimizing utilization of beta-lactam surgical prophylaxis through implementation of a structured allergy assessment tool in a presurgical clinic.

In patients with β-lactam allergies, administration of non-β-lactam surgical prophylaxis is associated with increased risk of infection. Although many patients self-report β-lactam allergies, most are unconfirmed or mislabeled. A quality improvement process, utilizing a structured β-lactam allergy tool, was implemented to improve the utilization of preferred β-lactam surgical prophylaxis.

Coinfection with Leishmania major and Staphylococcus aureus enhances the pathologic responses to both microbes through a pathway involving IL-17A.

Cutaneous leishmaniasis (CL) is a parasitic disease causing chronic, ulcerating skin lesions. Most humans infected with the causative Leishmania protozoa are asymptomatic. Leishmania spp.

NOD-like receptor C4 Inflammasome Regulates the Growth of Colon Cancer Liver Metastasis in NAFLD.

Nonalcoholic fatty liver disease (NAFLD) enhances the growth and recurrence of colorectal cancer (CRC) liver metastasis. With the rising prevalence of NAFLD, a better understanding of the molecular mechanism underlying NAFLD-associated liver metastasis is crucial. Tumor-associated macrophages (TAMs) constitute a large portion of the tumor microenvironment that promotes tumor growth.

Dendritic cell NLRC4 regulates influenza A virus-specific CD4 T cell responses through FasL expression.

Influenza A virus (IAV)-specific T cell responses are important correlates of protection during primary and subsequent infections. Generation and maintenance of robust IAV-specific T cell responses relies on T cell interactions with dendritic cells (DCs). In this study, we explore the role of nucleotide-binding domain leucine-rich repeat containing receptor family member NLRC4 in modulating the DC phenotype during IAV infection.