The vacuolar anti- activity of neutrophil primary granule peptidyl-arginine deiminase enzymes.

The role of neutrophils in host defense involves several cell processes including phagocytosis, degranulation of antimicrobial proteins, and the release of neutrophil extracellular traps (NETs). In turn, dysregulated cell activity is associated with the pathogenesis of airway and rheumatic diseases, in which neutrophil-derived enzymes including peptidyl-arginine deiminases (PADs) play a role. Known physiological functions of PADs in neutrophils are limited to the activity of PAD isotype 4 in histone citrullination in NET formation.

The activity of a Ga(III) catecholate complex against Aspergillus fumigatus in conditions mimicking cystic fibrosis lung and inhaled formulations for its pulmonary administration.

Azole-resistant Aspergillus fumigatus (A. fumigatus) is an emerging worldwide pathogen. Pulmonary aspergillosis primarily affects severely immunocompromised patients and is also a particularly critical condition for cystic fibrosis (CF) patients.

Quantitative proteomic analysis reveals Ga(III) polypyridyl catecholate complexes disrupt Aspergillus fumigatus mitochondrial function.

Infections caused by the airborne fungal pathogen, Aspergillus fumigatus, are increasing in severity due to growing numbers of immunocompromised individuals and the increasing incidence of antifungal drug resistance, exacerbating treatment challenges. Gallium has proven to be a strong candidate in the fight against microbial pathogens due to its iron-mimicking capability and substitution of Ga(III) in place of Fe(III), disrupting iron-dependent pathways. Since the antimicrobial properties of 2,2'-bipyridine and derivatives have been previously reported, we assessed the in vitro activity and proteomic effects of a recently reported heteroleptic Ga(III) polypyridyl catecholate compound against A.

Draft genome sequence of the fungal biocontrol agent, Kos.

Here, we report the draft genome sequence of strain Kos, isolated from casing soil used during cultivation in Dublin, Ireland. Kos exhibits a suppressive ability toward , , and , which are common threats to production, cultivation, and quality.

A First-in-Class Pyrazole-isoxazole Enhanced Antifungal Activity of Voriconazole: Synergy Studies in an Azole-Resistant Strain, Computational Investigation and in Vivo Validation in a Fungal Infection Model.

The widespread and irrational use of azole antifungal agents has led to an increase of azole-resistant strains with an urgent need for combination drug therapy, enhancing the treatment efficacy. Here, we report the discovery of a first-in-class pyrazole-isoxazole, namely, , that showed remarkable growth inhibition against the . ATCC 10231 strain in combination with voriconazole, acting as a downregulator of ERG 11 () gene expression with a significant reduction of the yeast-to-hypha morphological transition.

Viewpoint: The impending pandemic of resistant organisms - a paradigm shift towards source control is needed.

The United States needs a paradigm shift in its approach to control infectious diseases. Current recommendations are often made in a siloed feedback loop. This may be the driver for such actions as the abandonment of contact precautions in some settings, the allowance of nursing home residents who are carriers of known pathogens to mingle with others in their facility, and the determination of an intervention's feasibility based upon budgetary rather than health considerations for patients and staff.

Healthcare Violence and the Potential Promises and Harms of Artificial Intelligence.

Currently, the healthcare workplace is one of the most dangerous in the United States. Over a 3-month period in 2022, two nurses were assaulted every hour. Artificial intelligence (AI) has the potential to prevent workplace violence by developing unique patient insights through accessing almost instantly a patient's medical history, past institutional encounters, and possibly even their social media posts.

Characterization of secretome during sublethal infection of larvae.

The fungal pathogen can induce prolonged colonization of the lungs of susceptible patients, resulting in conditions such as allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis. Analysis of the secretome released during sub-lethal infection of larvae may give an insight into products released during prolonged human colonisation. larvae were infected with and the metabolism of host carbohydrate and proteins and production of fungal virulence factors were analysed.

Long COVID's Impact on Patients, Workers, & Society: A review.

The incidence of long COVID in adult survivors of an acute SARS-CoV-2 infection is approximately 11%. Of those afflicted, 26% have difficulty with day-to-day activities. The majority of long COIVD cases occur after mild or asymptomatic acute infection.

Viewpoint: Patient safety in primary care - patients are not just a beneficiary but a critical component in its achievement.

Promoting and maintaining patient safety in primary care requires different strategies and monitoring than utilized in large healthcare delivery systems. Maintenance of a culture of safety is key to providing patient safety but has been difficult to measure in primary care. This is particularly true in rural settings where practice size is a major barrier to measurement reliability.

Synthesis, characterisation and antibacterial activity of novel Ga(III) polypyridyl catecholate complexes.

Ga(III) polypyridyl catecholate complexes of type [Ga(bipy)(O,O)](NO) or [Ga(phen)(O,O)](NO) respectively were readily synthesised on reaction of Ga(NO) in methanol with 1 equivalent of catecholate ligand (2,3-DHBA, 3,4-DHBA, 2,3,4-THBA or CafA) and then 2 equivalents of either bipy or phen. The complexes were characterised in full including by X-ray crystallography, which established that the catecholate ligands coordinate the Ga(III) centres in a bidentate manner the two deprotonated hydroxy groups. All Ga(III) complexes exhibited good antibacterial activity against the Gram-negative pathogenic bacteria , and .

Synthesis, characterisation, and solution behaviour of Ag(I) bis(phenanthroline-oxazine) complexes and the evaluation of their biological activity against the pathogenic yeast Candida albicans.

Three Ag(I) bis(phenanthroline-oxazine) complexes with varying lipophilicity were synthesised and characterised. The solution stoichiometry of 1:2 Ag(I):ligand was determined for each complex by the continuous variation Job's plot method using NMR spectroscopy. NMR studies were also carried out to investigate the fluxional behaviour of the Ag(I) complexes in solution.

Structural and Spectroscopic Study of New Copper(II) and Zinc(II) Complexes of Coumarin Oxyacetate Ligands and Determination of Their Antimicrobial Activity.

Tackling antimicrobial resistance is of increasing concern in a post-pandemic world where overuse of antibiotics has increased the threat of another pandemic caused by antimicrobial-resistant pathogens. Derivatives of coumarins, a naturally occurring bioactive compound, and its metal complexes have proven therapeutic potential as antimicrobial agents and in this study a series of copper(II) and zinc(II) complexes of coumarin oxyacetate ligands were synthesised and characterised by spectroscopic techniques (IR, H, C NMR, UV-Vis) and by X-ray crystallography for two of the zinc complexes. The experimental spectroscopic data were then interpreted on the basis of molecular structure modelling and subsequent spectra simulation using the density functional theory method to identify the coordination mode in solution for the metal ions in the complexes.

Frontline Worker Safety in the Age of COVID-19: A Global Perspective.

The third annual Health Watch USA sm webinar conference assembled 16 speakers from 4 continents who shared information regarding frontline worker safety in the age of COVID-19. The U.S.

Prolonged Subculturing of on Extract Agar Results in Altered Virulence and Sensitivity to Antifungal Agents.

is an environmental saprophyte and opportunistic fungal pathogen of humans. The aim of the work presented here was to examine the effect of serially subculturing on agar generated from larvae in order to characterize the alterations in the phenotypes that might occur. The passaged strains showed alterations in virulence, antifungal susceptibility, and in protein abundances that may indicate adaptation after 25 passages over 231 days on extract agar.

Exposure of to Culture Filtrate Inhibits Growth and Stimulates Gliotoxin Production.

is an opportunistic fungal pathogen capable of inducing chronic and acute infection in susceptible patients. interacts with numerous bacteria that compose the microbiota of the lung, including and , both of which are common isolates from cystic fibrosis sputum. Exposure of to culture filtrate reduced fungal growth and increased gliotoxin production.

and Display Differential Proteomic Responses to the Silver(I) Compound, SBC3.

The urgent need to combat antibiotic resistance and develop novel antimicrobial therapies has triggered studies on novel metal-based formulations. -heterocyclic carbene (NHC) complexes coordinate transition metals to generate a broad range of anticancer and/or antimicrobial agents, with ongoing efforts being made to enhance the lipophilicity and drug stability. The lead silver(I) acetate complex, 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) (SBC3), has previously demonstrated promising growth and biofilm-inhibiting properties.

Omics-based analysis of honey bee (Apis mellifera) response to Varroa sp. parasitisation and associated factors reveals changes impairing winter bee generation.

The extensive annual loss of honey bees (Apis mellifera L.) represents a global problem affecting agriculture and biodiversity. The parasitic mite Varroa destructor, associated with viral co-infections, plays a key role in this loss.

Success and failures in MRSA infection control during the COVID-19 pandemic.

Private sector facilities in the United States have experienced a resurgence of Methicillin-resistant Staphylococcus aureus (MRSA) hospital-onset infections during the COVID-19 pandemic, which eliminated all gains that were achieved over the last decade. The third quarter of 2021, the Standardized Infection Ratio for hospital onset MRSA bloodstream infections was 1.17, well above the baseline value of 1.

Do buprenorphine doses and ratios matter in medication assisted treatment adherence.

Introduction: Buprenorphine (BUP), generally prescribed as buprenorphine/naloxone, is a key component of medication-assisted treatment (MAT) to manage opioid use disorder. Studies suggest higher doses of BUP increase treatment adherence. Routine urine drug screens (UDS) assist in monitoring MAT adherence via measurement of excreted BUP and its metabolite, norbuprenorphine (NBP).

Design, Synthesis and Mechanistic Studies of Novel Isatin-Pyrazole Hydrazone Conjugates as Selective and Potent Bacterial MetAP Inhibitors.

Methionine aminopeptidases (MetAPs) are attractive drug targets due to their essential role in eukaryotes as well as prokaryotic cells. In this study, biochemical assays were performed on newly synthesized Isatin-pyrazole hydrazones () to identify potent and selective bacterial MetAP inhibitors. Compound inhibited prokaryotic MetAP, i.

Histamine Produced by Gram-Negative Bacteria Impairs Neutrophil's Antimicrobial Response by Engaging the Histamine 2 Receptor.

We found that histamine (10-9 M) did not have any effect on the in vitro capture of Escherichia coli by neutrophils but accelerated its intracellular killing. In contrast, histamine (10-6 M) delayed the capture of Escherichia coli by neutrophils and reduced the amounts of pHrodo zymosan particles inside acidic mature phagosomes. Histamine acted through the H4R and the H2R, which are coupled to the Src family tyrosine kinases or the cAMP/protein kinase A pathway, respectively.

Exposure of Candida parapsilosis to the silver(I) compound SBC3 induces alterations in the proteome and reduced virulence.

The antimicrobial properties of silver have been exploited for many centuries and continue to gain interest in the fight against antimicrobial drug resistance. The broad-spectrum activity and low toxicity of silver have led to its incorporation into a wide range of novel antimicrobial agents, including N-heterocyclic carbene (NHC) complexes. The antimicrobial activity and in vivo efficacy of the NHC silver(I) acetate complex SBC3, derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*), have previously been demonstrated, although the mode(s) of action of SBC3 remains to be fully elucidated.

Novel detection method involving non-invasive sebum collection and next-generation sequencing.

Introduction: mites are common human ectoparasites found across a broad geographical range. They reside in pilosebaceous units of the skin and feed on sebum, epithelial and glandular cells. is the more common mite, inhabiting the upper end of the pilosebaceous unit while resides deeper in the skin and meibomian glands.