Efficacy of therapeutically administered gepotidacin in a rabbit model of inhalational anthrax.

is a Gram-positive Centers for Disease Control and Prevention category "A" biothreat pathogen. Without early treatment, inhalation of anthrax spores with progression to inhalational anthrax disease is associated with high fatality rates. Gepotidacin is a novel first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and is being evaluated for use against biothreat and conventional pathogens.

Efficacy of Intravenously Administered Gepotidacin in Cynomolgus Macaques following a Francisella tularensis Inhalational Challenge.

Francisella tularensis (F. tularensis) is a Centers for Disease Control (CDC) category "A" Gram-negative biothreat pathogen. Inhalation of F.

Fostemsavir and ethinyl estradiol drug interaction: Clinical recommendations for co-administration.

Objectives: Fostemsavir, a prodrug of temsavir, is indicated for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection, antiretroviral (ARV) intolerance, or safety considerations. Understanding drug-drug interactions (DDIs) is important in individuals taking fostemsavir with hormonal contraceptives or menopausal or gender-affirming hormonal therapies.

Methods: Effect of temsavir (active moiety) on the pharmacokinetics of ethinyl estradiol (EE) and norethindrone (NET) was evaluated in an open-label, single-sequence, four-cycle, four-treatment study in 26 healthy female participants (study 206279, NCT02480881).

Gepotidacin is efficacious in a nonhuman primate model of pneumonic plague.

Gepotidacin is a first-in-class triazaacenaphthylene antibacterial agent that selectively inhibits bacterial DNA gyrase and topoisomerase IV through a unique binding mode and has the potential to treat a number of bacterial diseases. Development of this new agent to treat pneumonic plague caused by depends on the U.S.

Week 96 Genotypic and Phenotypic Results of the Fostemsavir Phase 3 BRIGHTE Study in Heavily Treatment-Experienced Adults Living with Multidrug-Resistant HIV-1.

In the phase 3 BRIGHTE study in heavily treatment-experienced adults with multidrug-resistant HIV-1, fostemsavir plus optimized background therapy (OBT) resulted in sustained rates of virologic suppression through 96 weeks. HIV-1 RNA <40 copies/mL was achieved in 163/272 (60%) Randomized Cohort (RC) participants (with 1 or 2 remaining approved fully active antiretrovirals) and 37/99 (37%) Non-randomized Cohort (NRC) participants (with 0 fully active antiretrovirals). Here we report genotypic and phenotypic analyses of HIV-1 samples from 63/272 (23%) RC participants and 49/99 (49%) NRC participants who met protocol-defined virologic failure (PDVF) criteria through Week 96.

Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Temsavir, the Active Moiety of Fostemsavir.

The oral prodrug fostemsavir (GSK3684394, formerly BMS-663068) is an antiretroviral treatment for HIV-1. Fostemsavir is metabolized to its active moiety, temsavir, a first-in-class HIV-1 attachment inhibitor that binds to the viral envelope glycoprotein 120. Long-term antiretroviral therapy, the resulting longer life expectancy, and/or certain coinfections can increase the risk of chronic liver and kidney disease in HIV-1-infected individuals.

Equiprobable discrete models of site-specific substitution rates underestimate the extent of rate variability.

It is standard practice to model site-to-site variability of substitution rates by discretizing a continuous distribution into a small number, K, of equiprobable rate categories. We demonstrate that the variance of this discretized distribution has an upper bound determined solely by the choice of K and the mean of the distribution. This bound can introduce biases into statistical inference, especially when estimating parameters governing site-to-site variability of substitution rates.

Safety and tolerability of eltrombopag versus placebo for treatment of thrombocytopenia in patients with advanced myelodysplastic syndromes or acute myeloid leukaemia: a multicentre, randomised, placebo-controlled, double-blind, phase 1/2 trial.

Background: Patients with myelodysplastic syndrome or acute myeloid leukaemia who are thrombocytopenic and unable to receive disease-modifying therapy have few treatment options. Platelet transfusions provide transient benefit and are limited by alloimmunisation. Eltrombopag, an oral thrombopoietin receptor agonist, increases platelet counts and has preclinical antileukaemic activity.

Bacterial diversity in two Neonatal Intensive Care Units (NICUs).

Infants in Neonatal Intensive Care Units (NICUs) are particularly susceptible to opportunistic infection. Infected infants have high mortality rates, and survivors often suffer life-long neurological disorders. The causes of many NICU infections go undiagnosed, and there is debate as to the importance of inanimate hospital environments (IHEs) in the spread of infections.

Consequences of dichotomization.

Dichotomization is the transformation of a continuous outcome (response) to a binary outcome. This approach, while somewhat common, is harmful from the viewpoint of statistical estimation and hypothesis testing. We show that this leads to loss of information, which can be large.

A retrospective analysis of placentas from twin pregnancies derived from assisted reproductive technology.

There are conflicting studies associating twin pregnancies derived from assisted reproductive technology (ART) with preterm birth, low birthweight, and other negative outcomes. This work investigates whether ART is linked with any placental pathology, given that placentation significantly influences fetal development. A 5-year, retrospective cohort study was conducted on placentas from twin pregnancies.

Evolutionary model selection with a genetic algorithm: a case study using stem RNA.

The choice of a probabilistic model to describe sequence evolution can and should be justified. Underfitting the data through the use of overly simplistic models may miss out on interesting phenomena and lead to incorrect inferences. Overfitting the data with models that are too complex may ascribe biological meaning to statistical artifacts and result in falsely significant findings.

The role of placental pathology in the evaluation of interpersonal violence: a case of abdominal gunshot wound in a 27-week gravid uterus.

We present a 17-year-old G1P0 Asian American woman with a previously undiagnosed pregnancy who sustained an intra-abdominal gunshot wound at 27 weeks' gestation. Within 2 hours of the traumatic event, the victim was taken emergently to the operating room for exploratory laparotomy. Findings included a gravid uterus with two entrance wounds and two small exit wounds with active bleeding from the right broad ligament.

A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome.

Objective: Infants with meconium aspiration syndrome (MAS) have marked surfactant dysfunction. Airways and alveoli of affected neonates contain meconium, inflammatory cells, inflammatory mediators, edema fluid, protein, and other debris. The objective of this study was to compare treatment with bronchoalveolar lavage using dilute Surfaxin with standard therapy in a population of newborn infants with MAS.