Pharmacodynamics of NOSO-502 studied in vitro and in vivo: determination of the dominant pharmacodynamic index driver.

Background: NOSO-5O2 is the first clinical candidate of a new antimicrobial class-the odilorhabdins. The pharmacodynamics of NOSO-502 were studied in vitro and in vivo to establish the pharmacodynamic index (PDI) driver.

Methods: A dilutional pharmacokinetic system was used for in vitro experiments.

Probing the Design Rules for Optimizing Electron Spin Relaxation in Densely Packed Triplet Media for Quantum Applications.

Quantum technologies using electron spins have the advantage of employing chemical qubit media with tunable properties. The principal objective of material engineers is to enhance photoexcited spin yields and quantum spin relaxation. In this study, we demonstrate a facile synthetic approach to control spin properties in charge-transfer cocrystals consisting of 1,2,4,5-tetracyanobenzene (TCNB) and acetylated anthracene.

Room-Temperature Optically Detected Coherent Control of Molecular Spins.

Optically interfaced molecular spins are a promising platform for quantum sensing and imaging. Key for such applications is optically detecting coherent spin manipulation at room temperature. Here, using the photoexcited triplet state of organic chromophores (pentacene doped in p-terphenyl), we optically detect coherent spin manipulation with photoluminescence contrasts exceeding 15% at room temperature, both in a molecular crystal and thin film.

Pharmacodynamics of taniborbactam in combination with cefepime studied in an in vitro model of infection.

Objectives: To define the in vitro pharmacodynamics of taniborbactam against Enterobacterales with CTXM-15, KPC, AmpC, and OXA-48 β-lactamases.

Methods: An in vitro pharmacokinetic model was used to simulate serum concentrations associated with cefepime 2G by 1 h infusion 8 h. Taniborbactam was given in exposure ranging and fractionation simulations.

activity of cefiderocol against European Enterobacterales, including isolates resistant to meropenem and recentβ-lactam/β-lactamase inhibitor combinations.

Unlabelled: Carbapenem-resistant Enterobacterales represent a major health threat and have few approved therapeutic options. Enterobacterales isolates were collected from hospitalized inpatients from 49 sites in six European countries (1 January-31 December 2020) and underwent susceptibility testing to cefiderocol and β-lactam/β-lactamase inhibitor combinations. Meropenem-resistant (MIC >8 mg/L) and cefiderocol-susceptible isolates were analyzed by PCR, and cefiderocol-‍resistant isolates by whole-genome sequencing, to identify resistance mechanisms.

Investigating the impact of the COVID-19 pandemic on older adolescents' psychological wellbeing and self-identified cognitive difficulties.

Background: The COVID-19 pandemic coincides with growing concern regarding the mental health of young people. Older adolescents have faced a particular set of pandemic-related challenges and demonstrate heightened vulnerability to affective disorders (particularly anxiety). Anxiety symptoms are associated with a range of cognitive difficulties.

Exposure of Escherichia coli to antibiotic-efflux pump inhibitor combinations in a pharmacokinetic model: impact on bacterial clearance and drug resistance.

Background: Efflux pump inhibitors (EPIs) offer an attractive therapeutic option when combined with existing classes. However, their optimal dosing strategies are unknown.

Methods: MICs of ciprofloxacin (CIP)+/-chlorpromazine, phenylalanine-arginine β naphthylamide (PAβN) and a developmental molecule MBX-4191 were determined and the pharmacodynamics (PD) was studied in an in vitro model employing Escherichia coli MG1655 and its isogenic MarR mutant (I1147).

Antibacterial effect of seven days exposure to ceftolozane-tazobactam as monotherapy and in combination with fosfomycin or tobramycin against Pseudomonas aeruginosa with ceftolozane-tazobactam MICs at or above 4 mg/l in an in vitro pharmacokinetic model.

Objectives: To use a pre-clinical pharmacokinetic infection model to assess the antibacterial effect of ceftolozane/tazobactam alone or in combination with fosfomycin or tobramycin against Pseudomonas aeruginosa strains with MICs at or higher than the clinical breakpoint (MIC ≥ 4 mg/L).

Methods: An in vitro model was used to assess changes in bacterial load and population profiles after exposure to mean human serum concentrations of ceftolozane/tazobactam associated with doses of 2 g/1 g q8h, fosfomycin concentrations associated with doses of 8 g q8h or tobramycin at doses of 7 mg/kg q24 h over 168 h.

Results: Simulations of ceftolozane/tazobactam at 2 g/1 g q8h alone produced 3.

When perfection isn't enough: host egg signatures are an effective defence against high-fidelity African cuckoo mimicry.

Most mimicry systems involve imperfect mimicry, whereas perfect and high-fidelity mimicry are rare. When the fidelity of mimicry is high, mimics might be expected to have the upper hand against their antagonists. However, in coevolving systems, diversification of model phenotypes may provide an evolutionary escape, because mimics cannot simultaneously match all model individuals in the population.

N-Heteroacenes as an Organic Gain Medium for Room-Temperature Masers.

The development of future quantum devices such as the maser, i.e., the microwave analog of the laser, could be well-served by the exploration of chemically tunable organic materials.

Move Aside Pentacene: Diazapentacene-Doped para-Terphenyl, a Zero-Field Room-Temperature Maser with Strong Coupling for Cavity Quantum Electrodynamics.

Masers can deliver ultralow-noise amplification of microwave signals in medical imaging and deep-space communication, with recent research being rekindled through the discovery of gain media operating at room-temperature, eschewing bulky cryogenics that hindered their use. This work shows the discovery of 6,13-diazapentacene doped in para-terphenyl (DAP:PTP) as a maser gain medium that can operate at room-temperature, without an external magnetic field. With a maser output power of -10 dBm, it is on par with pentacene-doped para-terphenyl in masing power, while possessing compelling advantages such as faster amplification startup times, being pumped by longer wavelength light at 620 nm and greater chemical stability from nitrogen groups.

Lexical access speed and the development of phonological recoding during immediate serial recall.

A recent Registered Replication Report (RRR) of the development of verbal rehearsal during serial recall (Elliott et al., 2021) revealed that children verbalized at younger ages than previously thought (Flavell et al., 1966), but did not identify sources of individual differences.

Aggressive hosts are undeterred by a cuckoo's hawk mimicry, but probably make good foster parents.

Parasites face a trade-off if the highest quality hosts are also most resistant to exploitation. For brood parasites, well-defended host nests may be both harder to parasitize and harder to predate, leading to better survival of parasitic chicks. This trade-off could be accentuated if brood-parasitic adaptations to reduce front-line defences of hosts, such as mimicry of hawks by cuckoos, do not deter hosts which aggressively mob raptors.

Safeguarding human-wildlife cooperation.

Human-wildlife cooperation occurs when humans and free-living wild animals actively coordinate their behavior to achieve a mutually beneficial outcome. These interactions provide important benefits to both the human and wildlife communities involved, have wider impacts on the local ecosystem, and represent a unique intersection of human and animal cultures. The remaining active forms are human-honeyguide and human-dolphin cooperation, but these are at risk of joining several inactive forms (including human-wolf and human-orca cooperation).

Exploring Cluster-Dependent Antibacterial Activities and Resistance Pathways of NOSO-502 and Colistin against Enterobacter cloacae Complex Species.

The Enterobacter cloacae complex (ECC) is a group of diverse environmental and clinically relevant bacterial species associated with a variety of infections in humans. ECC have emerged as one of the leading causes of nosocomial infections worldwide. The purpose of this paper is to evaluate the activity of NOSO-502 and colistin (CST) against a panel of ECC clinical isolates, including different Hoffmann's clusters strains, and to investigate the associated resistance mechanisms.

The regulatory role of AP-2β in monoaminergic neurotransmitter systems: insights on its signalling pathway, linked disorders and theragnostic potential.

Monoaminergic neurotransmitter systems play a central role in neuronal function and behaviour. Dysregulation of these systems gives rise to neuropsychiatric and neurodegenerative disorders with high prevalence and societal burden, collectively termed monoamine neurotransmitter disorders (MNDs). Despite extensive research, the transcriptional regulation of monoaminergic neurotransmitter systems is not fully explored.

Evaluation of perturbed iron-homeostasis in a prospective cohort of patients with COVID-19.

Marked reductions in serum iron concentrations are commonly induced during the acute phase of infection. This phenomenon, termed hypoferremia of inflammation, leads to inflammatory anemia, but could also have broader pathophysiological implications. In patients with coronavirus disease 2019 (COVID-19), hypoferremia is associated with disease severity and poorer outcomes, although there are few reported cohorts.

Acylcarnitines: Nomenclature, Biomarkers, Therapeutic Potential, Drug Targets, and Clinical Trials.

Acylcarnitines are fatty acid metabolites that play important roles in many cellular energy metabolism pathways. They have historically been used as important diagnostic markers for inborn errors of fatty acid oxidation and are being intensively studied as markers of energy metabolism, deficits in mitochondrial and peroxisomal -oxidation activity, insulin resistance, and physical activity. Acylcarnitines are increasingly being identified as important indicators in metabolic studies of many diseases, including metabolic disorders, cardiovascular diseases, diabetes, depression, neurologic disorders, and certain cancers.

Advances in the development of new biomarkers for Alzheimer's disease.

Alzheimer's disease (AD) is a complex, heterogeneous, progressive disease and is the most common type of neurodegenerative dementia. The prevalence of AD is expected to increase as the population ages, placing an additional burden on national healthcare systems. There is a large need for new diagnostic tests that can detect AD at an early stage with high specificity at relatively low cost.

Comparative bactericidal activity of representative β-lactams against Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa.

Background: There is surprisingly little comparative published data on the bactericidal action of different sub-classes of β-lactams against aerobic Gram-negative rods, and the assumption is that all behave in the same way.

Objectives: To describe a systematic investigation of a representative penicillin, cephalosporin, monobactam and carbapenem against Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa.

Methods: Concentration-time-kill curves (TKC) were determined for three strains each of E.