Engineered Recombinant Hagfish Intermediate Filament Proteins: Unraveling Domain Roles in Synthetic Fiber Formation and Mechanics.

Hagfish intermediate filament (HIF) proteins, consisting of α and γ subunits, have been previously recombinantly expressed, purified, and utilized to form dry fibers with impressive mechanical properties. HIFα and HIFγ consist of three protein domains (N-termini, C-termini, and central rod domain). To begin to understand the structure-function relationship between the protein domains in fiber formation and properties in a synthetic fiber spinning system, we designed recombinant protein constructs with varying combinations of the N-terminus, central rod domain (CRD), and C-terminus for both the α and γ proteins.

In Vitro and In Vivo Studies on a Mononuclear Ruthenium Complex Reveals It is a Highly Effective, Fast-Acting, Broad-Spectrum Antimicrobial in Physiologically Relevant Conditions.

The crystal structure of a previously reported antimicrobial Ru complex that targets bacterial DNA is presented. Studies utilizing clinical isolates of Gram-negative bacteria that cause catheter-associated urinary tract infection, (CA)UTI, in media that model urine and plasma reveal that good antimicrobial activity is maintained in all conditions tested. Experiments with a series of clinical isolates show that, unlike the majority of previously reported Ru-based antimicrobial leads, the compound retains its potent activity even in MRSA strains.

A Qualitative Exploration of the Career-Choice Journey of Women in Anesthesiology.

Background: Women are underrepresented in the anesthesiology physician workforce. Additionally, recruitment of women into the specialty has been stagnant over the past 2 decades. Current evidence is lacking regarding how and why women navigate the career-exploration journey to find anesthesiology.

Medically Managed Lyme Periprosthetic Joint Infection: A Case Report.

Arthritis associated with Lyme disease is frequent in regions of the United States where the illness is widespread; nonetheless, periprosthetic joint infections (PJI) caused by Lyme are exceptionally rare. As of October 2023, only five cases of Lyme PJI have been documented in the literature. Four of these cases were managed successfully with surgical intervention, while one was managed successfully with oral and IV antibiotics.

Building a regional pediatric asthma learning health system in support of optimal, equitable outcomes.

Introduction: Asthma is characterized by preventable morbidity, cost, and inequity. We sought to build an Asthma Learning Health System (ALHS) to coordinate regional pediatric asthma improvement activities.

Methods: We generated quantitative and qualitative insights pertinent to a better, more equitable care delivery system.

Anesthesiologists and Community Engagement: A Scoping Review of the Literature.

Millions of individuals require anesthesia services each year. Although anesthesia-associated mortality rates have declined, anesthetic-related morbidity remains high, particularly among vulnerable populations. Disparities in perioperative screening, optimization, surveillance, and follow-up contribute to worse outcomes in these populations.

The INSIGHT project: reflections on the co-production of a quality recognition programme to showcase excellence in public involvement in health and care research.

Background: The quality of Patient and Public Involvement (PPI) in healthcare research varies considerably and is frequently tokenistic. We aimed to co-produce the Insight | Public Involvement Quality Recognition and Awards programme, based on the UK Standards for Public Involvement (UKSPI) alongside an incremental scale designed by Expert Citizens (a lived experience-led community group), to incentivise and celebrate continuous improvement in PPI.

Methods: We used Task and Finish Groups (19/44 [43%] public contributor membership) to co-produce the programme which we piloted in three organisations with different healthcare research models.

Clearing an ESKAPE Pathogen in a Model Organism; A Polypyridyl Ruthenium(II) Complex Theranostic that Treats a Resistant Acinetobacter baumannii Infection in Galleria mellonella.

In previous studies we have described the therapeutic action of luminescent dinuclear ruthenium(II) complexes based on the tetrapyridylphenazine, tpphz, bridging ligand on pathogenic strains of Escherichia coli and Enterococcus faecalis. Herein, the antimicrobial activity of the complex against pernicious Gram-negative ESKAPE pathogenic strains of Acinetobacter baumannii (AB12, AB16, AB184 and AB210) and Pseudomonas aeruginosa (PA2017, PA_ 007_ IMP and PA_ 004_ CRCN) are reported. Estimated minimum inhibitory concentrations and minimum bactericidal concentrations for the complexes revealed the complex shows potent activity against all A.

A Ruthenium(II) Polypyridyl Complex Disrupts Actin Cytoskeleton Assembly and Blocks Cytokinesis.

The dinuclear Ru complex [(Ru(phen))(tpphz)] (phen=1,10-phenanthroline, tpphz=tetrapyridophenazine) "RuRuPhen" blocks the transformation of G-actin monomers to F-actin filaments with no disassembly of pre-formed F-actin. Molecular docking studies indicate multiple RuRuPhen molecules bind to the surface of G-actin but not the binding pockets of established actin polymerisation inhibitors. In cells, addition of RuRuPhen causes rapid disruption to actin stress fibre organisation, compromising actomyosin contractility and cell motility; due to this effect RuRuPhen interferes with late-stage cytokinesis.

A Ruthenium(II) Polypyridyl Complex Disrupts Actin Cytoskeleton Assembly and Blocks Cytokinesis.

The dinuclear Ru complex [(Ru(phen) ) (tpphz)] (phen=1,10-phenanthroline, tpphz=tetrapyridophenazine) "RuRuPhen" blocks the transformation of G-actin monomers to F-actin filaments with no disassembly of pre-formed F-actin. Molecular docking studies indicate multiple RuRuPhen molecules bind to the surface of G-actin but not the binding pockets of established actin polymerisation inhibitors. In cells, addition of RuRuPhen causes rapid disruption to actin stress fibre organisation, compromising actomyosin contractility and cell motility; due to this effect RuRuPhen interferes with late-stage cytokinesis.

A Minimal Load-and-Lock Ru Luminescent DNA Probe.

Threading intercalators bind DNA with high affinities. Here, we describe single-molecule studies on a cell-permeant luminescent dinuclear ruthenium(II) complex that has been previously shown to thread only into short, unstable duplex structures. Using optical tweezers and confocal microscopy, we show that this complex threads and locks into force-extended duplex DNA in a two-step mechanism.

Spinal Cord Tumor Surgery.

A spinal cord tumor is any tumor involving the spinal cord or immediate surrounding area. Tumors typically are classified as extradural, intradural extramedullary, or intramedullary intradural. Many spinal cord tumor resections attempt to balance tumor removal with preservation of neurologic function.

Ruthenium based antimicrobial theranostics - using nanoscopy to identify therapeutic targets and resistance mechanisms in .

In previous studies we reported that specific dinuclear Ru complexes are particularly active against pathogenic Gram-negative bacteria and, unusually for this class of compounds, appeared to display lowered activity against Gram-positive bacteria. With the aim of identifying resistance mechanisms specific to Gram-positive bacteria, the uptake and antimicrobial activity of the lead complex against SH1000 and other isolates, including MRSA was investigated. This revealed differential, strain specific, sensitivity to the complex.

A Dinuclear Ruthenium(II) Complex Excited by Near-Infrared Light through Two-Photon Absorption Induces Phototoxicity Deep within Hypoxic Regions of Melanoma Cancer Spheroids.

The dinuclear photo-oxidizing Ru complex [{Ru(TAP)}(tpphz)] (TAP = 1,4,5,8- tetraazaphenanthrene, tpphz = tetrapyrido[3,2-:2',3'-:3″,2''-:2‴,3'''-]phenazine), , is readily taken up by live cells localizing in mitochondria and nuclei. In this study, the two-photon absorption cross section of is quantified and its use as a two-photon absorbing phototherapeutic is reported. It was confirmed that the complex is readily photoexcited using near-infrared, NIR, and light through two-photon absorption, TPA.

Making the Right Link to Theranostics: The Photophysical and Biological Properties of Dinuclear Ru-Re dppz Complexes Depend on Their Tether.

The synthesis of new dinuclear complexes containing linked Ru(dppz) and Re(dppz) moieties is reported. The photophysical and biological properties of the new complex, which incorporates a ,'-bis(4-pyridylmethyl)-1,6-hexanediamine tether ligand, are compared to a previously reported Ru/Re complex linked by a simple dipyridyl alkane ligand. Although both complexes bind to DNA with similar affinities, steady-state and time-resolved photophysical studies reveal that the nature of the linker affects the excited state dynamics of the complexes and their DNA photocleavage properties.

Structural Investigation into the Threading Intercalation of a Chiral Dinuclear Ruthenium(II) Polypyridyl Complex through a B-DNA Oligonucleotide.

Herein we report the separation of the three stereoisomers of the DNA light-switch compound [{Ru(bpy)}(tpphz)] (tpphz = tetrapyrido[3,2-a:2',3'-c:3″,2″-h:2‴,3‴-j]phenazine) by column chromatography and the characterization of each stereoisomer by X-ray crystallography. The interaction of these compounds with a DNA octanucleotide d(GCATATCG).d(CGATATGC) has been studied using NMR techniques.

Exploring the Cytotoxicity, Uptake, Cellular Response, and Proteomics of Mono- and Dinuclear DNA Light-Switch Complexes.

Drug resistance to platinum chemotherapeutics targeting DNA often involves abrogation of apoptosis and has emerged as a significant challenge in modern, non-targeted chemotherapy. Consequently, there is great interest in the anti-cancer properties of metal complexes-particularly those that interact with DNA-and mechanisms of consequent cell death. Herein we compare a parent cytotoxic complex, [Ru(phen)(tpphz)] [phen = 1,10-phenanthroline, tpphz = tetrapyridyl[3,2- a:2',3'- c:3″,2″- h:2‴,3‴- j]phenazine], with a mononuclear analogue with a modified intercalating ligand, [Ru(phen)(taptp)] [taptp = 4,5,9,18-tetraazaphenanthreno[9,10- b] triphenylene], and two structurally related dinuclear, tpphz-bridged, heterometallic complexes, RuRe and RuPt.

Results of a Flipped Classroom Teaching Approach in Anesthesiology Residents.

Background: In a flipped classroom approach, learners view educational content prior to class and engage in active learning during didactic sessions.

Objective: We hypothesized that a flipped classroom improves knowledge acquisition and retention for residents compared to traditional lecture, and that residents prefer this approach.

Methods: We completed 2 iterations of a study in 2014 and 2015.

Protective role of p450 epoxyeicosanoids in subarachnoid hemorrhage.

Background: Patients recovering from aneurysmal subarachnoid hemorrhage (SAH) are at risk for developing delayed cerebral ischemia (DCI). Experimental and human studies implicate the vasoconstrictor P450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) in the pathogenesis of DCI. To date, no studies have evaluated the role of vasodilator epoxyeicosatrienoic acids (EETs) in DCI.

Sex stratified neuronal cultures to study ischemic cell death pathways.

Sex differences in neuronal susceptibility to ischemic injury and neurodegenerative disease have long been observed, but the signaling mechanisms responsible for those differences remain unclear. Primary disassociated embryonic neuronal culture provides a simplified experimental model with which to investigate the neuronal cell signaling involved in cell death as a result of ischemia or disease; however, most neuronal cultures used in research today are mixed sex. Researchers can and do test the effects of sex steroid treatment in mixed sex neuronal cultures in models of neuronal injury and disease, but accumulating evidence suggests that the female brain responds to androgens, estrogens, and progesterone differently than the male brain.

Mechanism of the sex difference in endothelial dysfunction after stroke.

Stroke, the number four cause of death in the United States, is a greatly debilitating event resulting from insufficient blood supply to the brain (cerebral ischemia). Endothelial dysfunction, primarily characterized by dampened endothelial- dependent vasodilation, is a major contributor to the development and outcome of stroke. This review discusses the role of soluble epoxide hydrolase (sEH), an enzyme responsible for the degradation of vasoprotective eicosatrienoic acids (EETs), in the context of the cerebral vasculature and its contribution to the sexual dimorphic nature of stroke.

Mechanism of the sex difference in neuronal ischemic cell death.

Background: Stroke risk and outcome are different in men and women. We hypothesized that this is partly due to an inherent difference in susceptibility to ischemia between neurons from male vs. female brains.

Selective methoxy ether cleavage of 2,6-dimethoxyphenol followed by a selective acylation.

A Friedel-Crafts reaction of 2,6-dimethoxyphenol in the presence of aluminum chloride and propanoyl or butanoyl chlorid, respectively, lead, at elevated temperatures, to a selective cleavage of one of the methoxy groups followed by a selective acylation of the meta position with respect to the phenolic hydroxyl group. Under the same reaction conditions 2-methoxyphenol doesn't get demethylated; a mechanism to account for these findings is proposed. This reaction gives access to a variety of ortho-acylated catechols.

Preconditioning and postconditioning for neuroprotection: the most recent evidence.

Stroke is a leading cause of morbidity and mortality, with perioperative stroke being an important complication in the practice of anaesthesia. Unfortunately, pharmacological treatment options are very limited and often not applicable in the perioperative period. The notion of applying a subtoxic stimulus prior to an otherwise lethal event is termed preconditioning.