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EVER206 (also known as SPR206) is a novel polymyxin analog that has shown in vitro potency and in vivo efficacy against multidrug-resistant (MDR) Gram-negative pathogens. This randomized, double-blinded, placebo-controlled, Phase I study evaluated the safety, tolerability, and pharmacokinetics of EVER206 in healthy Chinese subjects. After single administration of 50-300 mg EVER206, the Cmax ranged from 3.94 to 25.82 mg/L, and the AUC0-inf ranged from 12.42 to 101.67 h·mg/L. The plasma exposure displayed a linear relationship with the dose administered...

AIMS: Active cigarette smoking is a major risk factor for chronic obstructive pulmonary disease that remains elevated after cessation. Skeletal muscle dysfunction has been well documented after smoking, but little is known about cardiac adaptations to cigarette smoking. The underlying cellular and molecular cardiac adaptations, independent of confounding lifestyle factors, and time course of reversibility by smoking cessation remain unclear. We hypothesized that smoking negatively affects cardiac metabolism and induces local inflammation in mice, which do not readily reverse upon 2-week smoking cessation...

Soluble N -glycosyltransferase from Actinobacillus pleuropneumoniae (ApNGT) catalyzes the glycosylation of asparagine residues, and represents one of the most encouraging biocatalysts for N -glycoprotein production. Since the sugar tolerance of ApNGT is restricted to limited monosaccharides ( e.g. , Glc, GlcN, Gal, Xyl, and Man), tremendous efforts are devoted to expanding the substrate scope of ApNGT via enzyme engineering. However, rational design of novel NGT variants suffers from an elusive understanding of the substrate-binding process from a dynamic point of view...

INTRODUCTION: Corticosteroid injection effectively treats de Quervain disease, and due to the high prevalence of the intracompartmental septum in the first extensor compartment, ultrasound guidance improves injection accuracy. OBJECTIVE: To compare the effectiveness, adverse events, and the recurrence rate between ultrasound-guided and palpation-guided injection in patients with de Quervain disease. DESIGN: Prospective, single-blind, randomized controlled trial...

BACKGROUND: Limited data is available on Mpox breakthrough infections. PURPOSE: Investigate a Mpox breakthrough outbreak in three vaccinated individuals. METHODS: Study participants provided informed consent. Serology testing was performed in one involved individual (ID-1) using an in-house assay detecting anti-orthopoxvirus IgG. Whole genome sequencing (WGS) was carried out and compared to the reference sequence ON563414.3 (https://www.ncbi...

BACKGROUND: In response to the 2022 mpox outbreak in the United States, people with higher potential for exposure to mpox were recommended to receive two doses of the JYNNEOS vaccine. Vaccine safety was monitored using two complementary systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS) is a passive surveillance system that accepts reports of adverse events following vaccination. VAERS is capable of rapidly identifying rare adverse events and unusual reporting patterns...

BACKGROUND: Dysfunctional sensory gating in anxiety disorders, indexed by the failure to inhibit the P50 event-related potential (ERP) to repeated stimuli, has been linked to deficits in the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). AIMS/METHODS: This study, conducted in 30 healthy volunteers, examined the acute effects of GABAA (lorazepam: 1 mg) and GABAB receptor (baclofen: 10 mg) agonists on P50 measures of auditory sensory gating within a paired-stimulus (S1-S2) paradigm and assessed changes in gating in relation to self-ratings of anxiety...

Mitochondrial DNA is a valuable tool for population genetics and evolutionary studies in a wide range of organisms. With advancements in sequencing techniques, it's now possible to gain deeper insights into this molecule. By understanding how many genes there are, how they're organized within the molecule, identifying the presence of spacers, and analyzing the composition of the D-Loop, we can better grasp the rearrangements that play a crucial role in the evolutionary dynamics of mitochondrial DNA. Additionally, phylogenetic analyses benefit significantly from having access to a larger pool of mtDNA genes...

Interaction with chemicals, present in drugs, food, environments, and consumer goods, is an integral part of our everyday life. However, depending on the amount and duration, such interactions can also result in adverse effects. With the increase in computational methods, the in silico methods can offer significant benefits to both regulatory needs and requirements for risk assessments and the pharmaceutical industry to assess the safety profile of a chemical. Here, we present ProTox 3.0, which incorporates molecular similarity and machine-learning models for the prediction of 61 toxicity endpoints such as acute toxicity, organ toxicity, clinical toxicity, molecular-initiating events (MOE), adverse outcomes (Tox21) pathways, several other toxicological endpoints and toxicity off-targets...

BACKGROUND: Simplified ablation technologies for pulmonary vein isolation (PVI) are increasingly performed worldwide. One of the most common complications following PVI are vascular access-related complications. Lately, venous closure systems (VCS) were introduced into clinical practice, aiming to reduce the time of bedrest, to increase the patients' comfort and to reduce vascular access-related complications. AIMS: To compare the safety and efficacy of using a VCS to achieve haemostasis following single shot PVI to the actual standard of care (figure-of-eight suture and manual compression (MC))...

This study evaluated the cost-effectiveness of maribavir versus investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for post-transplant refractory cytomegalovirus (CMV) infection with or without resistance. A two-stage Markov model was designed using data from the SOLSTICE trial (NCT02931539), real-world multinational observational studies, and published literature. Stage 1 (0-78 weeks) comprised clinically significant CMV (csCMV), non-clinically significant CMV (n-csCMV), and dead states; stage 2 (78 weeks-lifetime) comprised alive and dead states...

Temporal dynamics of local cortical rhythms during acute pain remain largely unknown. The current study used a novel approach based on transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) to investigate evoked-oscillatory cortical activity during acute pain. Motor (M1) and dorsolateral prefrontal cortex (DLPFC) were probed by TMS, respectively, to record oscillatory power (event-related spectral perturbation and relative spectral power) and phase synchronization (inter-trial coherence) by 63 EEG channels during experimentally induced acute heat pain in 24 healthy participants...

Gemtuzumab ozogamicin (GO) is a CD33 monoclonal antibody-drug conjugate currently in use to treat myeloid malignancies. A unique adverse effect of this medication is destruction of CD33 positive macrophages resulting in reduced clearance of free hemoglobin leading to grossly red plasma. This build-up of free hemoglobin can potentially lead to end organ damage and prevent performance of clinically necessary laboratory evaluation. We present a case of a pediatric patient who developed this adverse effect and was successfully treated with therapeutic plasma exchange (TPE)...

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited. AIMS: The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment...

Understanding the behavior of colloidal phosphorus (Pcoll ) under anoxic conditions is pivotal for addressing soil phosphorus (P) mobilization and transport and its impact on nutrient cycling. Our study investigated Pcoll dynamics in acidic floodplain soil during a 30-day flooding event. The sudden oxic-to-anoxic shift led to a significant rise in pore-water Pcoll levels, which exceeded soluble P levels by more than 2.7-fold. Colloidal fractions transitioned from dispersed forms (<220 nm) to colloid-associated microaggregates (>220 nm), as confirmed by electron microscopy...

OBJECTIVE: In this retrospective cross-sectional real-world evidence study from the Danish Headache Center (DHC), a national tertiary headache center in Denmark, we sought to identify potential pharmacological agents for the treatment of new daily persistent headache (NDPH). BACKGROUND: NDPH is an enigmatic headache disorder with abrupt onset and chronic duration for which evidence-based treatments are lacking. NDPH is a diagnosis of exclusion, for which secondary headaches must be ruled out and the etiology remains idiopathic...

Peanut allergy affects about 1%-3% of the pediatric population in the world, with an important increase in the last decades. Nowadays, international guidelines recommend the early introduction of peanuts in the infant diet, with poor information about the quantity and the frequency of the intake. Allergen immunotherapy may represent the only therapeutic strategy able to modify the natural history of peanut allergy. In particular, oral immunotherapy showed the most promising results in terms of efficacy, but with significant rates of adverse reactions, mostly gastrointestinal...

BACKGROUND AND AIMS: Using thermal-based energy sources (radiofrequency energy (RF)/cryo energy) for catheter ablation is considered effective and safe when performing pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). However, treatment success remains limited and complications can occur due to the propagation of thermal energy into nontarget tissues. We aim to compare pulsed field ablation (PFA) with RF ablation in terms of efficacy and safety for patients with drug-resistant paroxysmal AF...

Antibody-mediated rejection (AMR) is a common cause of graft failure after pig-to-nonhuman primate organ transplantation, even when the graft is from a pig with multiple genetic modifications. The specific factors that initiate AMR are often uncertain. We report two cases of pig kidney transplantation into immunosuppressed baboons in which we identify novel factors associated with the initiation of AMR. In the first, membranous nephropathy was the initiating factor that was then associated with the apparent loss of the therapeutic anti-CD154 monoclonal antibody in the urine when severe proteinuria was present...

BACKGROUND AND AIM: Tip-in endoscopic mucosal resection (EMR) has a high en bloc resection rate for large colorectal neoplasms. However, non-experts' performance in Tip-in EMR has not been investigated. We investigated whether Tip-in EMR can be achieved effectively and safely even by non-experts. METHODS: This retrospective study included consecutive patients who underwent Tip-in EMR for 15-25 mm colorectal nonpedunculated neoplasms at a Japanese tertiary cancer center between January 2014 and December 2020...