Bench-Stable 2-Halopyridinium Ketene Hemiaminals as Reagents for the Synthesis of 2-Aminopyridine Derivatives.

2-Chloro-1-(1-ethoxyvinyl)pyridinium triflate and several other bench-stable -(1-alkoxyvinyl) 2-halopyridinium triflates have been developed as reagents for the synthesis of valuable 2-aminopyridine scaffolds via unusually mild SAr substitutions with amine nucleophiles. Advantages of this approach include an operationally simple mix-and-stir procedure at room temperature or mild heat and ambient atmosphere and without the need for transition metal catalysts, coupling reagents, or high-boiling solvents. The stable -(1-ethoxyvinyl) moiety serves as a dual SAr-activating group and pyridine -protecting group that can be cleaved under thermal, acidic, or oxidative conditions.

Phase 1 drug-drug interaction study to assess the effect of CYP3A4 inhibition and pan-CYP induction on the pharmacokinetics and safety of fosmanogepix in healthy participants.

Unlabelled: Immunocompromised patients are susceptible to fungal infections, and drug-drug interactions with antifungals may occur due to concomitant medications. Fosmanogepix [FMGX; active moiety manogepix (MGX)] targets glycosylphosphatidylinositol-anchored mannoprotein synthesis and maturation, essential for fungal virulence. This phase 1, fixed-sequence study in healthy participants evaluated the effect of strong CYP3A4 inhibitor itraconazole [Cohort 1 ( = 18); FMGX 500 mg intravenous (IV) twice a day (BID )+ itraconazole 200 mg oral once a day (QD)] and pan-CYP inducer rifampin [Cohort 2 ( = 18); FMGX 1,000 mg IV BID + rifampin 600 mg oral QD] on the pharmacokinetics of FMGX and MGX.

Pharmacokinetics, safety, and tolerability of fosmanogepix IV to oral switch and multiple IV doses in healthy participants.

Fosmanogepix [FMGX, APX001; active form: manogepix (MGX), APX001A] is a first-in-class, intravenous (IV)/oral antifungal currently being evaluated for invasive fungal disease treatment. Data from two phase 1, placebo-controlled studies [IV-oral switch (study 1) and multiple IV doses (study 2)] evaluating FMGX tolerability, and pharmacokinetics (PK) are presented. Healthy adults (study 1: 18-65 years; study 2: 18-55 years) were eligible (randomized 3:1 to FMGX: placebo).

Enhanced metabolic detoxification is associated with fluroxypyr resistance in .

Auxin-mimic herbicides chemically mimic the phytohormone indole-3-acetic-acid (IAA). Within the auxin-mimic herbicide class, the herbicide fluroxypyr has been extensively used to control kochia (). A 2014 field survey for herbicide resistance in kochia populations across Colorado identified a putative fluroxypyr-resistant (Flur-R) population that was assessed for response to fluroxypyr and dicamba (auxin-mimics), atrazine (photosystem II inhibitor), glyphosate (EPSPS inhibitor), and chlorsulfuron (acetolactate synthase inhibitor).

Phase 1b safety and pharmacokinetics of intravenous and oral fosmanogepix in patients with acute myeloid leukaemia and neutropenia.

Objectives: Fosmanogepix (APX001), a first-in-class, intravenous (IV) and oral (PO) antifungal prodrug, is being developed to treat invasive fungal diseases (IFDs). Manogepix (APX001A; active moiety) targets fungal glycosylphosphatidylinositol-anchored cell wall transfer protein 1, inhibiting cell wall synthesis causing loss of viability. This open-label, multicentre, Phase 1b study in patients with AML and neutropenia (absolute neutrophil count <500 cells/μL; >10 days) undergoing chemotherapy aimed to assess tolerability, safety and pharmacokinetics (PK) of IV and PO fosmanogepix.

Safety and Pharmacokinetics of Intravenous and Oral Fosmanogepix, a First-in-Class Antifungal Agent, in Healthy Volunteers.

Fosmanogepix (FMGX, APX001), a first-in-class, intravenous (i.v.) and oral (p.

Evaluation of the current understanding of the impact of climate change on coral physiology after three decades of experimental research.

After three decades of coral research on the impacts of climate change, there is a wide consensus on the adverse effects of heat-stress, but the impacts of ocean acidification (OA) are not well established. Using a review of published studies and an experimental analysis, we confirm the large species-specific component of the OA response, which predicts moderate impacts on coral physiology and pigmentation by 2100 (scenario-B1 or SSP2-4.5), in contrast with the severe disturbances induced by only +2 °C of thermal anomaly.

Awakening a Molecular Mummy: The Inter-and Intramolecular Photochemistry of Pyromellitic Diimides with Alkyl Carboxylates.

Pyromellitic acid diimides are not as chemically unreactive as conjecturable (and presupposed) from their numerous applications as electron acceptor units or electron carriers in molecular donor-acceptor dyads or triads. Similar to the corresponding phthalimides, electronically excited pyromellitic diimides oxidize alkyl carboxylates in aqueous solution via intermolecular electron transfer (PET) processes, which eventually results in radical-radical combination products, e.g.

Multiteam Systems in Long Duration Exploration Missions: A Qualitative Analysis of Key Characteristics and Challenges.

Given the unprecedented environment of long duration space exploration (LDSE), success simply cannot occur without the coordinated efforts of multiple teams, both in flight and on the ground. These multiteam systems (MTSs) are needed to achieve the complex and dynamic tasks of spaceflight missions that will be longer and more uncertain than any previously experienced. Accordingly, research is limited in terms of how to best coordinate these teams and their dynamics-and in particular, how to best prepare LDSE teams to work across time and space effectively.

Are donor-conceived people willing to use donors themselves? Insights from individuals conceived via donor-assisted reproduction.

Study Question: Are donor-conceived people (DCP) willing to utilize donor gametes themselves if unable to conceive spontaneously?

Summary Answer: The majority of DCP would consider or are undecided about utilizing donor gametes and those who would consider the utilization are more likely to have been told about their donor-conceived origins at a young age by a family member and have overall positive experiences as a DCP.

What Is Known Already: DCP view their donor conception as an important part of their self-identity and many desire contact with genetically related individuals. Additionally, many believe that sperm donation should only be practiced if identifying information on the donor is provided.

Evaluation of potential drug interactions with sodium zirconium cyclosilicate: a single-center, open-label, one sequence crossover study in healthy adults.

Background: Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is an oral potassium binder for the treatment of hyperkalemia in adults. SZC acts in the gastrointestinal tract and additionally binds hydrogen ions in acidic environments like the stomach, potentially transiently increasing gastric pH and leading to drug interactions with pH-sensitive drugs. This study assessed potential pharmacokinetic (PK) interactions between SZC and nine pH-sensitive drugs.

Overuse Elbow Injuries in Youth Gymnasts.

Background: Gymnastics is a unique sport that places significant loads across the growing elbow, resulting in unique overuse injuries, some of which are poorly described in the current literature.

Purpose: To provide a comprehensive review of the unique overuse elbow injuries seen in youth gymnasts and to provide an up-to-date synthesis of the available literature and clinical expertise guiding treatment decisions in this population.

Study Design: Narrative review.

Third-Generation W(CNAr) Photoreductants (CNAr = Fused-Ring and Alkynyl-Bridged Arylisocyanides).

Homoleptic tungsten(0) arylisocyanides possess photophysical and photochemical properties that rival those of archetypal ruthenium(II) and iridium(III) polypyridine complexes. Previous studies established that extending the π-system of 2,6-diisopropylphenylisocyanide (CNDipp) by coupling aryl substituents to the isocyanide functionality results in W(CNDippAr) oligoarylisocyanide complexes with greatly enhanced metal-to-ligand charge transfer (MLCT) excited-state properties relative to those of W(CNDipp). Extending electronic modifications to delineate additional design principles for this class of photosensitizers, herein we report a series of W(CNAr) compounds with naphthalene-based fused-ring (CN-1-(2-Pr)-Naph) and CNDipp-based alkynyl-bridged (CNDippAr) arylisocyanide ligands.

Orthopedic Injuries in Professional Surfers: A Retrospective Study at a Single Orthopedic Center.

Background: Literature regarding surfing injuries is scarce and most studies report a high number of minor injuries. Recent literature suggests that musculoskeletal injuries are more common than previously reported. In the mid 2000s, competitive surfing has seen an increase in aerial maneuvers, as they have become more highly rewarded by the judging panel, which may be contributing to a change in injury patterns.

Small-scale preparation of perfluorocarbon-nanoemulsions utilizing dual centrifugation.

Background: Perfluorocarbon-nanoemulsions (PFC-NE) made of PFC and phospholipids (PL) by homogenization are optimal for in vivo-F labelling of monocytes and subsequently of inflamed tissues in magnetic resonance imaging (MRI). Necessary requirements for in vivo use of PFC-NE are sterility, suitable droplet sizes and the absence of immune activating liposomes, which are a typical byproduct of the homogenization process.

Methods And Results: To meet these requirements, we developed an aseptic in-vial preparation technique for PFC-NE based on dual centrifugation (DC) by testing different PFC/phospholipid ratios as well as the application of additives.

Ultrasound markers for prediction of complex gastroschisis and adverse outcome: longitudinal prospective nationwide cohort study.

Objectives: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value.

Methods: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.

Using three-dimensional ultrasound in predicting complex gastroschisis: A longitudinal, prospective, multicenter cohort study.

Objective: To determine whether complex gastroschisis (ie, intestinal atresia, perforation, necrosis, or volvulus) can prenatally be distinguished from simple gastroschisis by fetal stomach volume and stomach-bladder distance, using three-dimensional (3D) ultrasound.

Methods: This multicenter prospective cohort study was conducted in the Netherlands between 2010 and 2015. Of seven university medical centers, we included the four centers that performed longitudinal 3D ultrasound measurements at a regular basis.

Evaluation of a novel screening method for fetal aneuploidy using cell-free DNA in maternal plasma.

Objective: To evaluate the test performance of a novel sequencing technology using molecular inversion probes applied to cell-free DNA screening for fetal aneuploidy.

Methods: Two cohorts were included in the evaluation; a risk-based cohort of women receiving diagnostic testing in the first and second trimesters was combined with stored samples from pregnancies with fetuses known to be aneuploid or euploid. All samples were blinded to testing personnel before being analyzed, and validation occurred after the study closed and results were merged.

Ocular Distribution of Cyclosporine Following Topical Administration of OTX-101 in New Zealand White Rabbits.

Evaluate the ocular distribution, tolerability, and systemic exposure of cyclosporine (CsA) in New Zealand white rabbits following topical administration of OTX-101, a novel, clear aqueous nanomicellar solution developed for the treatment of dry eye disease (DED). The study design included single- and repeat-dose phases. In the single-dose phase, rabbits received a single instillation of OTX-101 0.

Rational manufacturing of functionalized, long-term stable perfluorocarbon-nanoemulsions for site-specific F magnetic resonance imaging.

Background: Perfluorocarbon (PFC)-nanoemulsions (NE) are a convenient tool for F magnetic resonance imaging in cell and animal experiments. Typical preparation methods, like high-pressure homogenization or microfluidization, produce nanoemulsions in mL-scale. However, experiments usually require only miniscule amounts of PFC-NE, several 100 µL.

A phase 1, open-label, single-arm study evaluating the ocular safety of OTX-101 and systemic absorption of cyclosporine in healthy human volunteers.

Purpose: To evaluate the ocular safety of OTX-101 0.09% - a novel, nanomicellar, clear, aqueous solution of cyclosporine (CsA) - and to determine the systemic exposure to CsA following ophthalmic administration.

Patients And Methods: Healthy volunteers ≥18 years of age were recruited for participation in this phase 1, open-label, single-center, single-arm, study.