Emergency Department Use of Heart Failure-Exacerbating Medications in Patients with Chronic Heart Failure.

BACKGROUND: Use of heart failure-exacerbating medications (HFEMs) may lead to preventable episodes of acute decompensated heart failure (HF). HFEMs use is common in patients with HF, and there may be opportunities to reduce their use from the emergency department (ED). METHODS: We performed an observational study on patients with HF presenting to EDs within a healthcare system between 1 January 2016 and 31 December 2020. Patients with chronic HF were identified using diagnostic codes within the electronic health record. The cohort was restricted to ambulatory (i.e., discharged to home) ED encounters. Medications, either ordered in the ED or prescribed at ED discharge, were extracted from the medication administration record and identified as potential HFEMs based on the 2016 American Heart Association Scientific Statement. Descriptive statistics were used to summarize the prevalence of HFEM use during ambulatory ED encounters. Exploratory analyses to identify correlates of HFEM use were performed. RESULTS: The study cohort included 23,907 ED encounters. ED administration or prescription of HFEMs occurred during 20% of ambulatory ED encounters. HFEM administration in the ED (17%) was more common than HFEM prescription at ED discharge (6%). The most common HFEMs administered in the ED included nonsteroidal anti-inflammatory drugs (11%) and albuterol (7%). CONCLUSION: HFEM use is common in patients with HF seeking ED care, occurring in roughly one-fifth of ambulatory ED encounters. There may be opportunities to optimize medication use among patients with HF in the ED.

Heteroaryl derivatives of suvorexant as OX1R selective PET ligand candidates: Cu-mediated 18F-fluorination of boroxines, in vitro and initial in vivo evaluation.

BACKGROUND: The orexin receptor (OXR) plays a role in drug addiction and is aberrantly expressed in colorectal tumors. Subtype-selective OXR PET ligands suitable for in vivo use have not yet been reported. This work reports the development of 18F-labeled OXR PET ligand candidates derived from the OXR antagonist suvorexant and the OX1R-selective antagonist JH112. RESULTS: Computational analysis predicted that fluorine substitution (1e) and introduction of the fluorobenzothiazole scaffold (1f) would be suitable for maintaining high OX1R affinity. After multi-step synthesis of 1a-1f, in vitro OXR binding studies confirmed the molecular dynamics calculations and revealed single-digit nanomolar OX1R affinities for 1a-f, ranging from 0.69 to 2.5 nM. The benzothiazole 1f showed high OX1R affinity (Ki = 0.69 nM), along with 77-fold subtype selectivity over OX2R. Cu-mediated 18F-fluorination of boroxine precursors allowed for a shortened reaction time of 5 min to provide the non-selective OXR ligand [18F]1c and its selective OX1R congener [18F]1f in activity yields of 14% and 22%, respectively, within a total synthesis time of 52-76 min. [18F]1c and [18F]1f were stable in plasma and serum in vitro, with logD7.4 of 2.28 ([18F]1c) and 2.37 ([18F]1f), and high plasma protein binding of 66% and 77%, respectively. Dynamic PET imaging in rats showed similar brain uptake of [18F]1c (0.17%ID/g) and [18F]1f (0.15%ID/g). However, preinjection of suvorexant did not significantly block [18F]1c or [18F]1f uptake in the rat brain. Pretreatment with cyclosporine A to study the role of P-glycoprotein (P-gp) in limiting brain accumulation moderately increased brain uptake of [18F]1c and [18F]1f. Accordingly, in vitro experiments demonstrated that the P-gp inhibitor zosuquidar only moderately inhibited polarized, basal to apical transport of 1c (p < 0.05) and had no effect on the transport of 1f, indicating that P-gp does not play a relevant role in brain accumulation of [18F]1c and [18F]1f in vivo. CONCLUSIONS: The in vitro and in vivo results of [18F]1c and [18F]1f provide a solid basis for further development of suitable OXR PET ligands for brain imaging.

Arthroscopic Midcarpal Suture Anchor Repair of Dorsal Intercarpal Ligament Avulsion.

The dorsal intercarpal ligament (DICL) is crucial for carpal stability and is frequently associated with injuries to other carpal ligaments, notably the scapholunate and lunotriquetral interosseous ligaments. Although isolated DICL injuries are uncommon, they can manifest as ligament avulsions, bony avulsions, or attenuations from chronic injury. Surgical repair of isolated DICL tears may be necessary when conservative management fails. We have previously described the first isolated DICL avulsion from the scaphoid dorsal ridge, suggesting an arthroscopic repair via the radiocarpal joint. This article details a repair technique through the midcarpal joint.

Monitoring soil fauna with ecoacoustics.

Ecoacoustics-or acoustic ecology-aids in monitoring elusive and protected species in several ecological contexts. For example, passive acoustic monitoring (PAM), which involves autonomous acoustic sensors, is widely used to detect various taxonomic groups in terrestrial and aquatic ecosystems, from birds and bats to fish and cetaceans. Here, we illustrate the potential of ecoacoustics to monitor soil biodiversity (specifically fauna)-a crucial endeavour given that 59% of species live in soil yet 75% of soils are affected by degradation. We describe the sources of sound in the soil (e.g. biological, geological and anthropogenic) and the ability of acoustic technology to detect and differentiate between these sounds, highlighting opportunities and current gaps in knowledge. We also propose a roadmap for the future development of optimized hardware, analytical pipelines and experimental approaches. Soil ecoacoustics is an emerging field with considerable potential to improve soil biodiversity monitoring and 'soil health' diagnostics. Indeed, early studies suggest soil ecoacoustics can be successfully applied in various ecosystems (e.g. grasslands, temperate, tropical and arid forests) and land uses (e.g. agriculture, viticulture, natural and restored ecosystems). Given the low cost, minimal intrusiveness, and effectiveness in supporting soil biodiversity assessments and biosecurity risks, we advocate for the advancement of soil ecoacoustics for future land management applications.

Heterogeneity of HPV16 virus-like particles indicates a complex assembly energy surface.

Human Papillomavirus serotype 16 (HPV16) capsid protein (L1) pentamers canonically assemble into T = 7 icosahedral capsids. Such virus-like particles are the basis of the HPV vaccine. We examined assembly of L1 pentamers in response to pH, mild oxidants, and ionic strength and found a mixture of closed, roughly spherical structures from ∼20 to ∼70 nm in diameter, indicating the presence of many kinetically accessible energy minima. Using bulk and single particle techniques we observed that the size distribution changes but does not reach homogeneity. Though heterogenous in size, particles showed uniform responses to low ionic strength dissociation, thermal unfolding, and susceptibility to protease digestion. These assays suggest maturation over time, but at different rates. Cysteine oxidation further stabilized particles at early, but not late, times without changing general characteristics including thermal stability and protease digestion. These data show complex assembly paths to species of different sizes, but with locally similar interactions.

Branched Polymeric Prenucleation Assemblies Initiate Calcium Phosphate Precipitation.

The formation of crystalline calcium phosphate (CaP) has recently gained ample attention as it does not follow the classic nucleation-and-growth mechanism of solid formation. Instead, the precipitation mechanisms can involve numerous intermediates, including soluble prenucleation species. However, structural features, stability, and transformation of such solution-state precursors remain largely undisclosed. Herein, we report a detailed and comprehensive characterization of the sequential events involved in calcium phosphate crystallization starting from the very early prenucleation stage. We integrated an extensive set of time-resolved methods, including NMR, turbidimetry, SAXS, cryo-TEM, and calcium-potentiometry to show that CaP nucleation is initiated by the transformation of "branched" polymeric prenucleation assemblies into amorphous calcium phosphate spheres. Such a mineralization process starts with the spontaneous formation of so-called nanometric prenucleation clusters (PNCs) that later assemble into those branched polymeric assemblies without calcium ion uptake from the solution. Importantly, the branched macromolecular species are invisible to many techniques (NMR, turbidity, calcium-potentiometry) but can readily be evidenced by time-resolved SAXS. We find that these polymeric assemblies constitute the origin of amorphous calcium phosphate (ACP) precipitation through an unexpected process: spontaneous dissolution is followed by local densification of 100-200 nm wide domains leading to ACP spheres of similar size. Finally, we demonstrate that the timing of the successive events involved in the CaP mineralization pathway can be kinetically controlled by the Ca2+/Pi molar ratio, such that the lifetime of the soluble transient species can be increased up to hours when decreasing it.

Metal-based nanomaterials in aquatic environments: What do we know so far about their ecotoxicity?

The wide range of applications of nanomaterials (NM) in different fields has led to both uncontrolled production and release into environmental compartments, such as aquatic systems, where final disposal occurs. Some efforts have been made to estimate their concentrations in environmental matrices; however, little is known about the actual effects of environmental NM concentrations on biota. The aims of the present review are to (i) expose the state of the art of the most applied NM and their actual concentrations regarding how much is being released to the aquatic environment and which are the predicted ones; (ii) analyze the current literature to elucidate if the aforementioned conditions were proven to cause deleterious effects on the associated organisms; and (iii) identify gaps in the knowledge regarding whether the actual NM concentrations are harmful to aquatic biota. These novel materials are expected to being released into the environment in the range of hundreds to thousands of tons per year, with Si- and Ti-based NM being the two most important. The estimated environmental NM concentrations are in the low range of ng to µg/L, except for Ti-based ones, which concentrations reach values on the order of mg/L. Empirical information regarding the ecotoxicity of environmental NM concentrations mainly focused on metal-based NM, however, it resulted poor and unbalanced in terms of materials and test species. Given its high predicted environmental concentration in comparison with the others, the ecotoxicity of Ti-based NM has been well assessed in algae and fish, while little is known regarding other NM types. While only a few marine species were addressed, the freshwater species Daphnia magna and Danio rerio accounted for the majority of studies on invertebrate and fish groups, respectively. Most of the reported responses are related to oxidative stress. Overall, we consider that invertebrate groups are the most vulnerable, with emphasis on microcrustaceans, as environmentally realistic metal-based NM concentration even caused mortality in some species. In the case of fish, we assumed that environmental concentrations of Ti-based NM represent a growing concern and threat; however, further studies should be carried out by employing other kinds of NM. Furthermore, more ecotoxicological information is needed in the case of carbon-based NM, as they are expected to considerably increase in terms of released amounts and applications in the near future.

Terrestrial invertebrate hosts of human pathogens in urban ecosystems.

Terrestrial invertebrates in urban ecosystems are extremely species-rich, have many important roles in material flow and energy circulation, and are host to many human pathogens that pose threats to human health. These invertebrates are widely distributed in urban areas, including both out- and in-door environments. Consequently, humans are frequently in contact with them, which provides many opportunities for them to pose human health risks. However, comprehensive knowledge on human pathogen transfer via invertebrates is lacking, with research to date primarily focused on dipterans (e.g., mosquitoes, flies). Here, we take a broad taxonomic approach and review terrestrial invertebrate hosts (incl. mosquitoes, flies, termites, cockroaches, mites, ticks, earthworms, collembola, fleas, snails, and beetles) of human pathogens, with a focus on transmission pathways. We also discuss how urbanization and global warming are likely to influence the communities of invertebrate hosts and have flow-on risks to human health. Finally, we identify current research gaps and provide perspectives on future directions.

The Janus (dual) model of immunoglobulin isotype evolution: Conservation and plasticity are the defining paradigms.

The study of antibodies in jawed vertebrates (gnathostomes) provides every immunologist with a bird's eye view of how human immunoglobulins (Igs) came into existence and subsequently evolved into their present forms. It is a fascinating Darwinian history of conservation on the one hand and flexibility on the other, exemplified by the Ig heavy chain (H) isotypes IgM and IgD/W, respectively. The cartilaginous fish (e.g., sharks) Igs provide a glimpse of "how everything got off the ground," while the amphibians (e.g., the model Xenopus) reveal how the adaptive immune system made an about face with the emergence of Ig isotype switching and IgG-like structure/function. The evolution of mucosal Igs is a captivating account of malleability, convergence, and conservation, and a call to arms for future study! In between there are spellbinding chronicles of antibody evolution in each class of vertebrates and rather incredible stories of how antibodies can adapt to occupy niches, for example, single-domain variable regions, cold-adapted Igs, convergent mechanisms to dampen antibody function, provision of mucosal defense, and many more. The purpose here is not to provide an encyclopedic examination of antibody evolution, but rather to hit the high points and entice readers to appreciate how things "came to be."

Association of Victimization by Sex among Public Facing Bus and Subway Transit Workers, New York City.

Federal data indicate that assaults on transit workers resulting in fatalities or hospitalizations tripled between 2008 and 2022. The data indicated a peri-pandemic surge of assault-related fatalities and hospitalizations, but assaults with less dire outcomes were not recorded. In collaboration with the Transport Workers Union, Local 100, we conducted an online survey in late 2023 through early 2024 of New York City public-facing bus and subway workers that focused on their work experiences during the 2020-2023 period of the COVID-19 pandemic. Items for this analysis on victimization included measures of physical and sexual assault/harassment, verbal harassment/intimidation, theft, and demographic characteristics (e.g., sex, race, work division). We estimated separate modified Poisson models for each of the four outcomes, yielding prevalence ratios (PRs) and 95% confidence intervals (CIs). Potential interactions between variables with strong main effects in the adjusted model were further examined using product terms. Among 1297 respondents, 89.0% reported any victimization; respondents also reported physical assault (48.6%), sexual assault/harassment (6.3%), verbal harassment/intimidation (48.7%), and theft on the transit system (20.6%). Physical assault was significantly more common among women in the bus division compared to female subway workers, male bus workers, and male subway workers (adjusted PR (aPR) = 3.54; reference = male subway workers; Wald test p < .001). With the same reference group, sexual assault/harassment was more frequently reported among female subway workers (aPR = 5.15; Wald test, p < .001), but verbal assault/intimidation and experiencing theft were least common among women in the bus division (aPR = 0.22 and 0.13, respectively; Wald tests, p < .001). These data point to the need for greater attention to record and report on victimization against workers in both buses and subway.

The effect of charge screening for cationic surfactants on the rigidity of interfacial nanoparticle assemblies.

HYPOTHESIS: Functionalizing colloidal particles with oppositely charged surfactants is crucial for stabilizing emulsions, foams, all-liquid structures, and bijels. However, surfactants can reduce the attachment energy, the driving force for colloidal self-assembly at interfaces. An open question remains on how the inherent interfacial activity of cationic surfactants influences the interfacial rigidity of particle-laden interfaces. We hypothesize that charge screening among cationic surfactants regulates the rigidity of oil/water interfaces by reducing the attachment energy of nanoparticles. EXPERIMENTS: We investigate the interfacial rigidity of cetyltrimethylammonium bromide (CTAB) functionalized silica nanoparticles (Ludox® TMA) by analyzing the shape deformation of 1,4-butanediol diacrylate (BDA) droplets under varying salt and alcohol concentrations. The nanoparticle packing density is assessed using scanning electron microscopy. Attachment energy is characterized through interfacial tension measurements, three-phase contact angle analysis, and CTAB adsorption studies. We also examine the effects of interfacial rigidities on the structure of bijel films formed via roll-to-roll solvent transfer-induced phase separation (R2R-STrIPS) using confocal laser scanning microscopy. FINDINGS: Increasing salt and alcohol concentrations decrease the interfacial rigidity of CTAB-functionalized nanoparticle films by reducing the interfacial tension. The contact angle has a minor influence on the rigidity. These results indicate that CTAB charge screening weakens the nanoparticle attachment energy to the interface. Controlling the rigidity enables the mass production of bijel sheets with consistent flatness, which is crucial for their potential applications in catalysis, energy storage, tissue engineering, and filtration membranes.

On the role of antibody affinity and avidity in the IgE-mediated allergic response.

Type I hypersensitivity, also known as classical allergy, is mediated via allergen-specific IgE antibodies bound to type I FcR (FcεRI) on the surface of mast cells and basophils upon cross-linking by allergens. This IgE-mediated cellular activation may be blocked by allergen-specific IgG through multiple mechanisms, including direct neutralization of the allergen or engagement of the inhibitory receptor FcγRIIb which blocks IgE signal transduction. In addition, co-engagement of FcεRI and FcγRIIb by IgE-IgG-allergen immune complexes causes down regulation of receptor-bound IgE, resulting in desensitization of the cells. Both, activation of FcεRI by allergen-specific IgE and engagement of FcγRIIb by allergen-specific IgG are driven by allergen-binding. Here we delineate the distinct roles of antibody affinity versus avidity in driving these processes and discuss the role of IgG subclasses in inhibiting basophil and mast cell activation.

Charge Detection Mass Spectrometry Enables Molecular Characterization of Nucleic Acid Nanoparticles.

Nucleic acid nanoparticles (NANPs) are increasingly used in preclinical investigations as delivery vectors. Tools that can characterize assembly and assess quality will accelerate their development and clinical translation. Standard techniques used to characterize NANPs, like gel electrophoresis, lack the resolution for precise characterization. Here, we introduce the use of charge detection mass spectrometry (CD-MS) to characterize these materials. Using this technique, we determined the mass of NANPs varying in size, shape, and molecular mass, NANPs varying in production quality due to formulations lacking component oligonucleotides, and NANPs functionalized with protein and nucleic acid-based secondary molecules. Based on these demonstrations, CD-MS is a promising tool to precisely characterize NANPs, enabling more precise assessments of the manufacturing and processing of these materials.

Poor compliance and exemptions facilitate ongoing deforestation.

Many nations are struggling to reduce deforestation, despite having extensive environmental protection laws in place and commitments to international agreements that address the biodiversity and climate crises. We developed a novel framework to quantify the extent to which contemporary deforestation is being captured under national and subnational laws. We then applied this framework to northern Australia as a case study, a development and deforestation hotspot with ecosystems of global significance. First, deforestation may be compliant under all relevant legislation, either through assessment and approval or because of exemptions in the legislation. Second, deforestation may be compliant under at least one relevant law, but not all. Third, there may be no evidence of deforestation assessment or exemption from assessment, despite their apparent requirement, which could mean the deforestation is potentially noncompliant. Finally, deforestation may occur in an area or under circumstances that are beyond the intended scope of any relevant legislation. All deforestation that we analyzed was hypothetically covered by one or more laws. However, 65% of deforestation was potentially noncompliant with at least one law. Because multiple laws could be relevant to a given clearing event, the majority of clearing was still compliant with at least one law, but of these events, only a small proportion was explicitly approved (19%). The remaining were permitted under various exemptions. Of all the legislation we analyzed, most of the exempt clearing occurred under one subnational law and most potentially noncompliant clearing occurred under one national law. Our results showed that even a nation with a suite of mature environmental protection laws is falling well short of achieving international commitments regarding deforestation. Our framework can be used to pinpoint the pathways of policy change required for nations to align local laws with these international accords.

Cumplimiento deficiente y exenciones que facilitan la deforestación Resumen Muchos países luchan por reducir la deforestación, a pesar de contar con amplias leyes de protección del medio ambiente y de sus compromisos con los acuerdos internacionales que abordan la crisis de la biodiversidad y el clima. Por ello desarrollamos un novedoso marco para cuantificar hasta qué punto la deforestación actual se recopila en las leyes nacionales y subnacionales. Después aplicamos este marco al norte de Australia como estudio de caso, un punto caliente de desarrollo y deforestación con ecosistemas de importancia mundial. En primer lugar, la deforestación puede ser compatible con toda la legislación pertinente, ya sea mediante evaluación y aprobación o debido a exenciones en la legislación. En segundo lugar, la deforestación puede ser compatible con al menos una ley pertinente, pero no con todas. En tercer lugar, puede que no haya pruebas de evaluación de la deforestación o de exención de la evaluación, a pesar de su aparente requisito, lo que podría significar que la deforestación es potencialmente no conforme. Por último, la deforestación puede producirse en una zona o en circunstancias que quedan fuera del ámbito de aplicación de la legislación pertinente. Toda la deforestación analizada era hipotéticamente legal según una o más leyes. Sin embargo, el 65% de la deforestación no cumplía potencialmente al menos una ley. Dado que varias leyes podían ser pertinentes para un determinado caso de deforestación, la mayoría de las deforestaciones seguían cumpliendo al menos una ley, pero de estos casos, sólo una pequeña proporción estaba explícitamente aprobada (19%). El resto estaba permitido en virtud de diversas exenciones. De toda la legislación que analizamos, la mayor parte de la compensación exenta se produjo en virtud de una ley subnacional y la mayor parte de la compensación potencialmente no conforme se produjo en virtud de una ley nacional. Nuestros resultados muestran que incluso un país con un conjunto de leyes maduras de protección del medio ambiente está muy lejos de cumplir los compromisos internacionales en materia de deforestación. Nuestro marco puede utilizarse para determinar las vías de cambio político necesarias para que los países adapten su legislación local a los acuerdos internacionales.

New Biomarkers for Renal Transporter-Mediated Drug-Drug Interactions: Metabolomic Effects of Cimetidine, Probenecid, Verapamil, and Rifampin in Humans.

The inhibition of renal transport proteins organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATE1, MATE2-K), and organic anion transporters (OAT1, OAT3) causes clinically relevant drug-drug interactions (DDI). Endogenous biomarkers could be used to improve risk prediction of such renal DDIs. While a number of biomarkers for renal DDIs have been described so far, multiple criteria for valid biomarkers have frequently not been investigated, for example, specificity, metabolism, or food effects. Therefore, there is a need for novel biomarkers of renal DDIs. Here, we investigated the global metabolomic effects following the administration of two classical inhibitors of renal transport proteins [cimetidine (OCT2/MATEs), probenecid (OATs)] in human plasma and urine of healthy volunteers. Additionally, we investigated metabolomic effects of two inhibitors of other transporters [verapamil (P-glycoprotein), rifampin (organic anion transporting polypeptides)] as controls. This analysis shows that both cimetidine and probenecid affect compounds involved in caffeine metabolism, carnitines, and sulfates. Hierarchical cluster analysis of the effects of all four inhibitors on endogenous compounds identified multiple promising new sensitive and specific biomarker candidates for OCT2/MATE- or OAT-mediated DDIs. For OCT2/MATEs, 5-amino valeric acid betaine (median log2-fold change of estimated renal elimination: -3.62) presented itself as a promising candidate. For OATs, estimated renal elimination of 7-methyluric acid and cinnamoylglycine (median log2-fold changes -3.10 and -1.92, respectively) was both sensitive and specific. This study provides comprehensive information on metabolomic effects of transport protein inhibition in humans and identifies putative new sensitive and specific biomarkers for renal transporter-mediated DDIs.

Realization of Higher Resolution Charge Detection Mass Spectrometry.

Charge detection mass spectrometry (CD-MS) allows mass distributions to be measured for heterogeneous samples that cannot be analyzed by conventional MS. With CD-MS, the m/z and charge are measured for individual ions using a detection cylinder embedded in an electrostatic linear ion trap (ELIT). Imprecision in both the m/z and charge measurements contribute to the mass resolution. However, if the charge can be measured with a precision of <0.2 e the charge state can be assigned with a low error rate and the mass resolving power only depends on the m/z resolution. Prior to this work, the best resolving power demonstrated experimentally for CD-MS was 700. Here we demonstrate a resolving power of >14,600, 20-times higher than the previous best. Trajectory simulations were used to optimize the geometry and electrostatic potentials of the ELIT. We found conditions where the energy dependence of the oscillation frequency becomes parabolic, and then operated with a nominal ion energy at the minimum of the parabola. The 14,600 resolving power was obtained with a beam collimator before the ELIT. With the collimator removed, the resolving power of the optimized ELIT is 7300, which is still an order of magnitude higher than the previous best. The resolving power was demonstrated by resolving the isotope distributions for peptides and proteins. High resolution CD-MS measurements were then used to resolve the glycans on a monoclonal antibody and applied to the analysis of hepatitis B virus capsids. The results indicate that procedures for adduct removal need to be improved for the full benefit of the higher resolving power to be realized for higher mass species. However, these results represent a key step toward using CD-MS to analyze very complex protein mixtures where charge states are not well resolved in the m/z spectrum because of congestion from numerous overlapping peaks.

Mapping the oral resistome: a systematic review.

Studying individual ecological niches within the oral cavity is a logical first step to understanding the distribution of antimicrobial resistance genes (ARGs); however, it is not representative of the whole oral resistome. The aim of our systematic review was to provide a map of the oral resistome by reviewing the composition of individual niches. A total of 580 papers were retrieved from a search of all English language publications investigating the presence of oral ARGs in five electronic databases between January 2015 and August 2023. Fifteen studies [10 PCR and 5 next-generation sequencing (NGS)] were included in this review. The heterogeneity of methods precluded meta-analysis. ARGs are present throughout the oral cavity with 158 unique ARGs identified across 6 locations - supra and sub-gingival biofilm, mucosa, oropharynx, root canal system (RCS) and saliva. The supragingival biofilm had the highest resistome richness, while the RCS had the least. Tetracycline was the dominant antimicrobial resistance (AMR) class found. Three core genes were identified - tet(M), tet(O) and ermB.This review highlights the necessity of NGS studies to comprehensively characterize the oral resistome in its entirety. This is the logical foundation for future 'omics studies to truly understand the scope of the resistome and its contribution to AMR.

Ecological phage therapy: Can bacteriophages help rapidly restore the soil microbiome?

Soil microbiota underpin ecosystem functionality yet are rarely targeted during ecosystem restoration. Soil microbiota recovery following native plant revegetation can take years to decades, while the effectiveness of soil inoculation treatments on microbiomes remains poorly explored. Therefore, innovative restoration treatments that target soil microbiota represent an opportunity to accelerate restoration outcomes. Here, we introduce the concept of ecological phage therapy-the application of phage for the targeted reduction of the most abundant and dominant bacterial taxa present in degraded ecosystems. We propose that naturally occurring bacteriophages-viruses that infect bacteria-could help rapidly shift soil microbiota towards target communities. Bacteriophages sculpt the microbiome by lysis of specific bacteria, and if followed by the addition of reference soil microbiota, such treatments could facilitate rapid reshaping of soil microbiota. Here, we experimentally tested this concept in a pilot study. We collected five replicate pre-treatment degraded soil samples, then three replicate soil samples 48 hours after phage, bacteria, and control treatments. Bacterial 16S rDNA sequencing showed that phage-treated soils had reduced bacterial diversity; however, when we combined ecological phage therapy with reference soil inoculation, we did not see a shift in soil bacterial community composition from degraded soil towards a reference-like community. Our pilot study provides early evidence that ecological phage therapy could help accelerate the reshaping of soil microbiota with the ultimate aim of reducing timeframes for ecosystem recovery. We recommend the next steps for ecological phage therapy be (a) developing appropriate risk assessment and management frameworks, and (b) focussing research effort on its practical application to maximise its accessibility to restoration practitioners.