Preclinical development and characterisation of PP353, a formulation of linezolid for intradiscal administration.

Introduction: Bacterial infection of the intervertebral disc can lead to vertebral endplate edema known as Modic changes, with associated chronic low back pain. Oral antimicrobial therapy has shown efficacy but relies on prolonged dosing and may not be optimal in terms of patient outcome, side effects, or antibiotic stewardship. There is no antibiotic formulation approved for intradiscal administration.

Optimization of the Central α-Amino Acid in Cystobactamids to the Broad-Spectrum, Resistance-Breaking Antibiotic CN-CC-861.

Cystobactamids have a unique oligoarylamide structure and exhibit broad-spectrum activity against Gram-negative and Gram-positive bacteria. In this study, the central α-amino acid of the cystobactamid scaffold was modified to address the relevance of stereochemistry, hydrogen bonding and polarity by 33 derivatives. As demonstrated by three matched molecular pairs, l-amino acids were preferred over d-amino acids.

Combinatorics and topological weights of chromatin loop networks.

Polymer physics models suggest that chromatin spontaneously folds into loop networks with transcription units (TUs), such as enhancers and promoters, as anchors. Here we use combinatoric arguments to enumerate the emergent chromatin loop networks, both in the case where TUs are labeled and where they are unlabeled. We then combine these mathematical results with those of computer simulations aimed at finding the inter-TU energy required to form a target loop network.

Topological Spectra and Entropy of Chromatin Loop Networks.

The 3D folding of a mammalian gene can be studied by a polymer model, where the chromatin fiber is represented by a semiflexible polymer which interacts with multivalent proteins, representing complexes of DNA-binding transcription factors and RNA polymerases. This physical model leads to the natural emergence of clusters of proteins and binding sites, accompanied by the folding of chromatin into a set of topologies, each associated with a different network of loops. Here, we combine numerics and analytics to first classify these networks and then find their relative importance or statistical weight, when the properties of the underlying polymer are those relevant to chromatin.

Quality of vision clinical outcomes for a new fully-refractive extended depth of focus Intraocular Lens.

Background/objective: To evaluate the visual performance of a purely refractive extended depth of focus (EDF) intraocular lens (IOL).

Subjects/methods: A prospective, multi-center, randomized, subject/evaluator-masked study. Subjects were bilaterally implanted with the EDF test (Model ZEN00V, TECNIS PureSee™ IOL, N = 60) or an enhanced monofocal control (Model ICB00, TECNIS Eyhance™ IOL, N = 57) IOL.

Studies of antibacterial activity (in vitro and in vivo) and mode of action for des-acyl tridecaptins (DATs).

Tridecaptins comprise a class of linear cationic lipopeptides with an N-terminal fatty acyl moiety. These 13-mer antimicrobial peptides consist of a combination of d- and l-amino acids, conferring increased proteolytic stability. Intriguingly, they are biosynthesized by non-ribosomal peptide synthetases in the same bacterial species that also produce the cyclic polymyxins displaying similar fatty acid tails.

Mechanisms of Post-Stroke Fatigue: A Follow-Up From the Third Stroke Recovery and Rehabilitation Roundtable.

Background: Post-stroke fatigue (PSF) is a significant and highly prevalent symptom, whose mechanisms are poorly understood. The third Stroke Recovery and Rehabilitation Roundtable paper on PSF focussed primarily on defining and measuring PSF while mechanisms were briefly discussed. This companion paper to the main paper is aimed at elaborating possible mechanisms of PSF.

Effect of High-Intensity Interval Training and Moderate-Intensity Continuous Training in People With Poststroke Gait Dysfunction: A Randomized Clinical Trial.

Background: The exercise strategy that yields the greatest improvement in both cardiorespiratory fitness () and walking capacity poststroke has not been determined. This study aimed to determine whether conventional moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) have different effects on and 6-minute walk distance (6MWD).

Methods And Results: In this 24-week superiority trial, people with poststroke gait dysfunction were randomized to MICT (5 days/week) or HIIT (3 days/week with 2 days/week of MICT).

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

Rationale: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities.

Methods: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts.

Enriched Rehabilitation Reduces Abnormal Motor Synergies and Enhances Motor Plasticity Following Severe Stroke in Rats.

Background: Stroke results in loss of upper motor neuron control over voluntary movements and emergence of abnormal synergies. Presently, it is unclear to what extent poststroke recovery reflects true recovery (restitution), compensation, or some combination of these processes. Here, we investigated this question using behavioral and kinematic analyses of skilled reaching in rats subjected to severe stroke that affected both the forelimb motor cortex and dorsolateral striatum.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

Rationale: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities.

Methods: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts.

Self-reported sleep disturbances among people who have had a stroke: a cross-sectional analysis.

Background: Sleep disturbances and their potential association with stroke remains understudied at a population level. We sought to determine the prevalence of sleep disturbances among people who have effects of stroke compared with the general population.

Methods: We used data from people aged 18 years or older who responded to the sleep and chronic disease modules of the 2017-2018 cycle of the Canadian Community Health Survey (CCHS).

Potential long-term disturbance associated with beach nourishment - insights and observations from Pea Island National Wildlife Refuge, Outer Banks, North Carolina.

The longer-term ecosystem impacts associated with a beach nourishment project conducted in 2014 were studied on an ocean beach on the Pea Island National Wildlife Refuge on North Carolina's Outer Banks. The unique nature of the project is tied to the study's duration, which spans nine years, and the venue, a national wildlife refuge where human-sourced confounding effects are minimal. Populations for five invertebrates: Emerita talpoida (the Atlantic Mole Crab), (the Coquina Clam), Scolelepis squamata, Ocypode quadrata (the Atlantic Ghost Crab), and indigenous Amphipods were monitored seasonally over nine-years that asymmetrically straddled the 2014 nourishment event.

Enhancing Diversity and Inclusion in Clinical Trials.

Women and people from most racial and ethnic groups in the United States have historically been under-represented in clinical trials of investigational medical products. Inadequate representation of these groups may lead to an incomplete understanding of the safety and efficacy of new drugs, devices, biologics, and vaccines, and limit the generalizability of trial findings. As a result, new medical products may not be beneficial to all people who need them, and existing inequities in outcomes among various population groups may remain unchanged or worsen, or new disparities may arise.

Active turbulence and spontaneous phase separation in inhomogeneous extensile active gels.

We report numerical results for the hydrodynamics of inhomogeneous lyotropic and extensile active nematic gels. By simulating the coupled Cahn-Hilliard, Navier-Stokes, and Beris-Edwards equation for the evolution of the composition, flow and orientational order of an active nematic, we ask whether composition variations are important to determine its emergent physics. As in active gels of uniform composition, we find that increasing either activity or nematic tendency (, overall active matter concentration) triggers a transition between an isotropic passive phase and an active nematic one.

Validity of Bioelectric Impedance in Relation to Dual-Energy X-Ray Absorptiometry for Measuring Baseline and Change in Body Composition After an Exercise Program in Stroke.

Vanzella, LM, Lawand, R, Shuaib, M, Oh, P, Corbett, D, and Marzolini, S. Validity of bioelectric impedance in relation to dual-energy x-ray absorptiometry for measuring baseline and change in body composition after an exercise program in stroke. J Strength Cond Res 36(12): 3273-3279, 2022-Exercise is an important strategy to improve fat-free mass (FFM) and reduce percent fat mass (FM%).

The impact of BCG strains and repeat vaccinations on immunodiagnostic tests in Eurasian badgers (Meles meles).

Bacille Calmette-Guerin (BCG) is a potential tool in the control of Mycobacterium bovis in European badgers (Meles meles). A five year Test and Vaccinate or Remove (TVR) research intervention project commenced in 2014 using two BCG strains (BCG Copenhagen 1331 (Years 1-3/ BadgerBCG) and BCG Sofia SL2222 (Years 4-5). Badgers were recaptured around 9 weeks after the Year 5 vaccination and then again a year later.

Slitrk2 deficiency causes hyperactivity with altered vestibular function and serotonergic dysregulation.

SLITRK2 encodes a transmembrane protein that modulates neurite outgrowth and synaptic activities and is implicated in bipolar disorder. Here, we addressed its physiological roles in mice. In the brain, the Slitrk2 protein was strongly detected in the hippocampus, vestibulocerebellum, and precerebellar nuclei-the vestibular-cerebellar-brainstem neural network including pontine gray and tegmental reticular nucleus.

Buildout and integration of an automated high-throughput CLIA laboratory for SARS-CoV-2 testing on a large urban campus.

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the first cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for COVID-19 testing which was costly, difficult to obtain, or had long turn-around times.

Comparison of 3-month visual outcomes of a new multifocal intraocular lens vs a trifocal intraocular lens.

Purpose: To compare the clinical performance of the TECNIS Synergy multifocal (model ZFR00V) intraocular lens (IOL) with that of the AcrySof PanOptix Trifocal (model TFNT00) IOL in patients undergoing bilateral cataract surgery.

Setting: Multicenter clinical setting.

Design: Prospective randomized comparative study.

Timing and Dose of Upper Limb Motor Intervention After Stroke: A Systematic Review.

This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors.

Discovery of Novel UDP--Acetylglucosamine Acyltransferase (LpxA) Inhibitors with Activity against .

This study describes a novel series of UDP--acetylglucosamine acyltransferase (LpxA) inhibitors that was identified through affinity-mediated selection from a DNA-encoded compound library. The original hit was a selective inhibitor of LpxA with no activity against LpxA. The biochemical potency of the series was optimized through an X-ray crystallography-supported medicinal chemistry program, resulting in compounds with nanomolar activity against LpxA (best half-maximal inhibitory concentration (IC) <5 nM) and cellular activity against (best minimal inhibitory concentration (MIC) of 4 μg/mL).