Bactericidal efficacy of low dose gaseous ozone against clinically relevant multidrug-resistant bacteria.

Introduction: Healthcare-associated infections (HAIs) pose a significant challenge in acute care hospitals, particularly in intensive care units, due to persistent environmental contamination despite existing disinfection protocols and manual cleaning methods. Current disinfection methods are labor-intensive and often ineffective against multidrug-resistant (MDR) pathogens, highlighting the need for new, automated, hands-free approaches.

Methods: This study evaluates the bactericidal efficacy of low concentrations of gaseous ozone (5 ppm) against clinically relevant and often MDR bacteria under various concentrations, contact times, temperatures, and environmental conditions.

Trends in Demographic Characteristics and Risk Factors among Individuals with Syphilis in Colorado from 2011-2020.

Background: Identify opportunities to improve syphilis screening by describing changes in patient characteristics and risk factors among individuals with syphilis and by comparing cases with and without an indication for syphilis screening.

Methods: This retrospective cohort study used Colorado public health surveillance data to identify 8,326 syphilis diagnoses from 2011-2020. Demographics, clinical characteristics, and risk factors were compared across 2-year groups and between individuals with and without an indication for screening.

Development of a physiologically-based pharmacokinetic model for Ritonavir characterizing exposure and drug interaction potential at both acute and steady-state conditions.

Ritonavir (RTV) is a potent CYP3A inhibitor that is widely used as a pharmacokinetic (PK) enhancer to increase exposure to select protease inhibitors. However, as a strong and complex perpetrator of CYP3A interactions, RTV can also enhance the exposure of other co-administered CYP3A substrates, potentially causing toxicity. Therefore, the prediction of drug-drug interactions (DDIs) and estimation of dosing requirements for concomitantly administered drugs is imperative.

Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5-HT Antagonist Antiemetic Drugs.

Cisplatin is a platinum-based chemotherapeutic drug used to treat many types of cancer. The aim of this study was to develop a population pharmacokinetic model that incorporates plasma unbound and bound platinum levels. Cancer patients undergoing their first or second cycle of cisplatin-containing chemotherapy (n = 33) were prospectively randomized to receive a 5-hydroxytryptamine (5-HT) antagonist (5-HTA) antiemetic (ondansetron, granisetron, or palonosetron) followed by blood collection over 10 days.

The epidemiology and clinical presentation of seropositive neuromyelitis optica spectrum disorder in a US population.

Objective: To define the epidemiology and clinical presentation of seropositive neuromyelitis optica spectrum disorder (NMOSD) in a large US health system.

Methods: We completed a retrospective observational study of adult patients in the University of Colorado Health System from 1 January 2011 to 31 December 2020, using Health Data Compass (HDC), a data warehouse that combines electronic health information with claims and public health data in Colorado. We screened HDC for patients with either (1) an abnormal aquaporin-4 IgG test or (2) any G36 ICD-10 code.

Investigating the role of Wnt3a and Wnt5a as critical factors of hepatic stellate cell activation in acute toxicant-induced liver injury.

Toxicant exposure can lead to acute liver injury, characterized by hepatic reprogramming and wound healing. Hepatic stellate cells (HSC) play a key role in liver regeneration during wound healing by secreting fibrogenic factors and production of extracellular matrix (ECM). However, repetitive injury to the liver can lead to extensive scarring and liver fibrosis, indicating HSCs coordinate both regeneration and disease.

Interaction of milrinone with extracorporeal life support.

Background: Milrinone is commonly prescribed to critically ill patients who need extracorporeal life support such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT). Currently, the effect of ECMO and CRRT on the disposition of milrinone is unknown.

Methods: Ex vivo ECMO and CRRT circuits were primed with human blood and then dosed with milrinone to study drug extraction by the circuits.

The Paradox of Antimalarial Terpenoid Isonitrile Biosynthesis Explained. Proposal of Cyanoformate as an NC Delivery Vector.

Marine sponge diterpenoid isonitriles are exceptional nitrogenous natural products that exhibit antiplasmodial activity. Their biosynthesis presents a biosynthetic puzzle: how do the elements of NC engage terpenyl carbocations in isoprenoid secondary metabolism, and what is the biosynthetic precursor of the NC group? Cyanoformic acid (NC-COOH, ) is proposed as a plausible delivery vehicle of NC that resolves a paradox in the commonly held proposition that an inorganic cyanide anion, CN, terminates terpenoid isonitrile (TI) biosynthesis. DFT calculations of NC-COOH and its conjugate base, cyanoformate, NC-COO (), support high nucleophilicity at N and explain bond-forming constitutionality: attack at N and formation of an isonitrile over its nitrile isomer.

The Cost of Continuous Glucose Monitoring Versus Self-Monitoring of Blood Glucose in Type 1 Diabetes Pregnancies in the United States: A Cost-Consequences Analysis Using Real-World Evidence.

Data on the cost implications of continuous glucose monitoring (CGM) use in type 1 diabetes (T1D) pregnancies in the United States are sparse. Drawing on associations identified in real-world evidence from a retrospective chart review at the Barbara Davis Center for Diabetes, we conducted a cost-consequences analysis of CGM use versus self-monitoring of blood glucose (SMBG), inclusive of neonatal intensive care unit (NICU) spending. In the base-case analysis assuming per-label CGM use and per-guideline finger-stick frequency, the per-person cost was $16,254 for CGM versus $15,182 for SMBG.

Sofosbuvir/Velpatasvir Pharmacokinetics, Safety, and Efficacy in Pregnant People with Hepatitis C Virus.

Background: Treatment of hepatitis C virus (HCV) during pregnancy can cure maternal HCV and prevent perinatal HCV transmission. The primary objective was to compare the pharmacokinetics (PK) of sofosbuvir/velpatasvir (SOF/VEL) in pregnant versus nonpregnant people.

Methods: Pregnant people with chronic HCV infection were enrolled between 23-25 weeks' gestation and were provided SOF/VEL daily for 12 weeks.

CHD1L Inhibitor OTI-611 Synergizes with Chemotherapy to Enhance Antitumor Efficacy and Prolong Survival in Colorectal Cancer Mouse Models.

Colorectal cancer (CRC) is one of the most prevalent and deadly forms of cancer. It is universally treated with a combination of the DNA damaging chemotherapy drugs irinotecan, 5-Fluorouracil (5-FU), and oxaliplatin. is a novel oncogene that plays critical roles in chromatin remodeling and DNA damage repair, as well as the regulation of malignant gene expression.

Immunization but not natural infection of horses results in antibody activity against the S protein of Streptococcus equi subsp equi.

Objective: Evaluate the immunogenicity of a vaccine targeting the S protein (Ssee) of Streptococcus equi subsp equi and determine antibody activity against Ssee in horses with strangles.

Methods: The study was designed as a prospective experiment using 20 university-owned Quarter Horses and a cross-sectional serosurvey of 78 privately owned horses with strangles. Horses were immunized IM with 0 (n = 4), 200 (n = 8), or 400 (n = 8) μg of recombinant Ssee at weeks 0, 4, and 12.

Pathobiont-driven antibody sialylation through IL-10 undermines vaccination.

The pathobiont Staphylococcus aureus (Sa) induces nonprotective antibody imprints that underlie ineffective staphylococcal vaccination. However, the mechanism by which Sa modifies antibody activity is not clear. Herein, we demonstrate that IL-10 is the decisive factor that abrogates antibody protection in mice.

Nanomolar activity of coumarin-3-thiosemicarbazones targeting Trypanosoma cruzi cruzain and the T. brucei cathepsin L-like protease.

Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) urgently demand innovative drug development due to their impact on public health worldwide.

Ruxolitinib-dependent reduction of seizure load and duration is accompanied by spatial memory improvement in the rat pilocarpine model of temporal lobe epilepsy.

Molecules with optimized pharmacokinetic properties selectively aimed at the inhibition of STAT3 phosphorylation in brain have recently emerged as potential disease modifying therapies for epilepsy. In the current study, pharmacological inhibition of JAK1/2 with the orally available, FDA-approved drug ruxolitinib, produced nearly complete inhibition of hippocampal STAT3 phosphorylation, and reduced the expression of its downstream target Cyclin D1, when administered to rats 30 ​min and 3 ​h after onset of pilocarpine-induced status epilepticus (SE). This effect was accompanied by significantly shorter seizure duration and lower overall seizure frequency throughout the 4 weeks of EEG recording, but did not completely prevent the development of epilepsy in ruxolitinib-treated male rats.

Sex-differences in reporting of statin-associated diabetes mellitus to the US Food and Drug Administration.

Introduction: Diabetes mellitus (DM) is increasingly recognized as a possible consequence of statin therapy. Secondary analysis of randomized clinical trials and limited observational cohort analyses have suggested that women may be more likely than men to experience statin-associated DM. No analyses of real-world drug safety data addressing this question have been published.

Specific surface-modified iron oxide nanoparticles trigger complement-dependent innate and adaptive antileukaemia immunity.

Considerable advances have been achieved in the application of nanomaterials for immunotherapies, yet the precise immune effects induced by protein corona remain elusive. Here, we explore the formation mechanism and immune regulation process of protein corona in acute myeloid leukaemia (AML) mouse models using commercialized iron oxide nanoparticles (IONPs), with different surface modifications, including an FDA-approved variant. Using macrophages depleted or Complement Component 3 (C3) knockout mice, we demonstrate that carboxymethyl dextran-coated IONP (IONP-COOH) reduces leukaemia burden.

Fear of missing out: Drug availability in the United States vs Canada.

Background: Per capita spending on drugs in the United States is double that of Canada. One commonly debated point when comparing the 2 countries is whether this additional spending allows residents of the United States access to valuable therapies not available in Canada.

Objective: To characterize the therapeutic value of prescription drugs used in the United States that are not marketed in Canada.

Outcomes of a multidisciplinary approach to management of mavacamten in obstructive hypertrophic cardiomyopathy.

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