Antimicrobials and antimicrobial resistance genes in the shadow of COVID-19 pandemic: A wastewater-based epidemiology perspective.

Higher usage of antimicrobial agents in both healthcare facilities and the communities has resulted in an increased spread of resistant bacteria. However, the improved infection prevention and control practices may also contribute to decreasing antimicrobial resistance (AMR). In the present study, wastewater-based epidemiology (WBE) approach was applied to explore the link between COVID-19 and the community usage of antimicrobials, as well as the prevalence of resistance genes. Longitudinal study has been conducted to monitor the levels of 50 antimicrobial agents (AAs), 24 metabolites, 5 antibiotic resistance genes (ARGs) and class 1 integrons (intI 1) in wastewater influents in 4 towns/cities over two years (April 2020 - March 2022) in the South-West of England (a total of 1,180 samples collected with 87,320 individual AA measurements and 8,148 ARG measurements). Results suggested higher loads of AAs and ARGs in 2021-22 than 2020-21, with beta-lactams, quinolones, macrolides and most ARGs showing statistical differences. In particular, the intI 1 gene (a proxy of environmental ARG pollution) showed a significant increase after the ease of the third national lockdown in England. Positive correlations for all quantifiable parent AAs and metabolites were observed, and consumption vs direct disposal of unused AAs has been identified via WBE. This work can help establish baselines for AMR status in communities, providing community-wide surveillance and evidence for informing public health interventions. Overall, studies focused on AMR from the start of the pandemic to the present, especially in the context of environmental settings, are of great importance to further understand the long-term impact of the pandemic on AMR.

Hands-On Activity Illustrating the Sorting Process of Recycled Waste and Its Role in Promoting Sustainable Solutions.

Effective recycling is not merely a matter of collecting waste; it also requires meticulous categorization to maximize the potential for reusing material and minimizing waste sent to landfills. Education and awareness of the sorting and recycling process bottlenecks need to be emphasized and extended beyond higher educational contexts (e.g., in multiple stages of educational pathways, such as middle or high school). Hence, this project introduces a hands-on plastic sorting activity where students use recycled waste to be sorted based on their physical properties. Several tools were provided to perform the separation, such as water, sieves, magnets, and manual/visual separation while considering the time and cost associated with each tool. The activity was evaluated by pre- and post-evaluations based on Likert-scale and open-ended questions grouped in several categories related to the sorting process. In several categories, we observed that the activity enhanced student knowledge (e.g., general sorting understanding), while in other categories, there was no growth. From open-ended questions, students expressed an understanding of how to sort recycled waste and an appreciation for the trade-offs in developing sorting solutions. This activity effectively enhanced students' awareness of the sorting process of recycled waste. It lays the foundation for future inquiry and outreach project design.

Increasing Naloxone Access and Prescribing for Patients on High-Dose Opioids From a Managed Care Pharmacy Health Plan Perspective.

Background: Opioid overdoses decrease when communities have access to naloxone. Clinicians play a key role in offering naloxone to high-risk chronic opioid patients. Managed care pharmacists within our health plan noted disproportionate processing for claims of opioid utilizers compared to claims of naloxone prescriptions. Objective: To increase naloxone access and prescribing to members who classify at a dosage with a higher risk for opioid overdose, defined as over 90 morphine milligram equivalents (MME). Methods: Multiple system-wide initiatives were implemented to improve naloxone access. A claims file was pulled monthly to identify members on opioids meeting MME criteria >90 MME per day excluding members with cancer, sickle cell disease, or on hospice. A separate report was then matched to naloxone claims and prescribing percentages calculated. Results: 12 444 utilizing members on opioids were identified from June 2019 prescription claims data. Of these, 131 were on opioids exceeding 90 MME per day, or 1.05% of utilizers, and the percentage of members exceeding 90 MME per day prescribed naloxone was 6.87%. By May 2023, the percentage of opioid utilizers exceeding 90 MME per day decreased to 0.58%. Naloxone prescribing increased to 41.18%. Conclusion: A multi-pronged approach to improve access to naloxone and continued educational efforts by our health plan increased naloxone prescribing in members on opioids exceeding 90 MME per day.

Pressure Indicator Composite Films via Compressive Deformation of a Translucent Matrix Containing a Contrasting Filler.

A neglected mechanism for pressure-responsive color change is demonstrated using cellulose acetate composites prepared by direct (solvent) immersion annealing (DIA), with different loadings of activated charcoal filler. Namely, compressive plastic deformation of the translucent cellulose acetate leads to a decrease in the optical path length and a concomitant increase in the visibility of the opaque contrasting filler. Composites bearing 1-7 wt% activated charcoal exhibited a linear relationship between applied pressure and resulting pressure mark brightness in the range of 12-56 MPa. Comparison of pressure mark patterns with cross-sectional scanning electron microscopy (SEM) supports the importance of the porous morphology arising from DIA for the tuning of the pressure indicator sensitivity. A simple ball drop test is used to illustrate the robustness and utility of these indicators in optical impact assessment.

Assessment of restriction measures implemented during COVID pandemics on community lifestyle choices via wastewater-based epidemiology.

SARS-CoV-2 pandemic affected lifestyle habits, and the mental health and wellbeing of people around the world. In this manuscript, two towns (Paulton and Radstock) and two cities (Bath and Bristol) in Southwest England (> 1 million people) were monitored for two years using Wastewater-Based Epidemiology to assess impacts of COVID (including management measures such as lockdowns and movement restrictions) on community lifestyle choices: illicit drugs, legal stimulants, abused pharmaceuticals and pain pharma usage. Results were triangulated with key dates captured during the pandemic (national lockdowns, restrictions and social distancing measures, etc.). This highlighted a reduction in cocaine intake (as benzoylecgonine) (community average: -36 %) during the first lockdown and an increase in illicit drugs usage after the 3rd national lockdown (community averages for amphetamine: +8 %, cocaine/benzoylecgonine: +39 %, ketamine:+70 %) when restrictions were removed, and social interaction and recreational activities increased. There was a reduction in the intake of caffeine (as 1,7-dimethylxanthine) (community average:-39 %) after 3rd national lockdown coinciding with pubs reopening while nicotine intake (via cotinine) remained stable indicating lack of impact of COVID on smoking habits. Pain pharma often used in pain management resulting from injuries linked with sport activities (naproxen and diclofenac) showed decrease in usage due to lockdown restrictions in physical exercise and access to gyms/sport facilities.

Understanding treatment of pain during SARS-CoV-2 pandemic in a two-year intercity longitudinal study using wastewater-based epidemiology.

SARS-CoV-2 pandemic had a significant impact on the society, economy, and health of people around the world with consequences that need to be better understood for future pandemic preparedness. This manuscript provides insights into the usage of pharmaceuticals for pain treatment management throughout SARS-CoV-2 pandemic. Four towns and cities with a total population of > 1 million people covering an area of 2000 km2 in South West England were monitored for twenty-four months. Results showed different patterns in pain pharma usage, with small towns having higher population normalised daily loads (PNDLs) than big cities for majority of pain killers studied. This is likely due to demographics of these cities with smaller cities having older population. Per capita consumption of non-steroidal anti-inflammatory drugs (NSAIDs) increased compared to pre-pandemic usage in line with SARS-CoV-2 infections (ibuprofen and acetaminophen), while body pain drugs (diclofenac and naproxen) decreased in line with restrictions and closure of sports facilities. Changes in population normalised daily intake (PNDI) of pain killers were particularly apparent during the 1st and 3rd national lockdown. Comparison of PNDIs with prescriptions highlighted differences related to medication availability (OTC drugs) and patients' nonadherence (prescribed drugs). In addition, several instances of direct disposal events across the catchments were observed which raises an issue of lack of pharma compliance and general understanding of potential environmental impacts from pharma usage.

Draft genome sequence of multidrug-resistant Vibrio navarrensis strain DA9 isolated from a coastal canal in the Florida Keys (USA).

A presumptive Vibrio isolate with a multidrug resistance profile was isolated from surface seawater collected from a coastal canal in 2014 and identified as Vibrio navarrensis, designated as strain DA9. Here, we report a 5.1-Mb draft genome sequence of strain DA9 with a G + C content of 47.5%.

Mu-opioid receptor knockout on Foxp2-expressing neurons leads to reduced aversion-resistant reward seeking.

Mu-opioid receptors (MORs) in the amygdala and striatum are important in addictive and rewarding behaviors. Foxp2 is a marker of intercalated (ITC) cells in the amygdala and a subset of striatal medium spiny neurons (MSNs), both of which express MORs in wild-type mice. For the current series of studies, we characterized the behavior of mice with genetic deletion of the MOR gene Oprm1 in Foxp2-expressing neurons (Foxp2-Cre/Oprm1 fl/fl ). Male and female Foxp2-Cre/Oprm1 fl/fl mice were generated and heterozygous Cre+ (knockout) and homozygous Cre-(control) animals were tested for aversion-resistant alcohol consumption using an intermittent access (IA) task, operant responding for a sucrose reward, conditioned place aversion (CPA) to morphine withdrawal, and locomotor sensitization to morphine. In IA, mice with the MOR-knockout were more sensitive to quinine-adulterated ethanol (EtOH) and less aversion-resistant, as they decreased EtOH consumption from baseline at all quinine concentrations, while control animals did not. In operant conditioning, Cre+ mice similarly exhibited less aversion-resistant reward seeking than Cre-mice when sucrose was adulterated with quinine. For CPA, both control and MOR-knockout mice demonstrated withdrawal-induced aversion. For locomotor sensitization, Cre+ mice demonstrated decreased locomotion following morphine injection compared to Cre-mice. The results of these studies suggest that MOR expression on Foxp2-expressing neurons is not necessary for rewarded behaviors or expression of opioid withdrawal but may be involved in aversion-resistance.

Direct wastewater extraction as a simple and effective method for SARS-CoV-2 surveillance and COVID-19 community-level monitoring.

Wastewater surveillance has proven to be an effective tool to monitor the transmission and emergence of infectious agents at a community scale. Workflows for wastewater surveillance generally rely on concentration steps to increase the probability of detection of low-abundance targets, but preconcentration can substantially increase the time and cost of analyses while also introducing additional loss of target during processing. To address some of these issues, we conducted a longitudinal study implementing a simplified workflow for SARS-CoV-2 detection from wastewater, using a direct column-based extraction approach. Composite influent wastewater samples were collected weekly for 1 year between June 2020 and June 2021 in Athens-Clarke County, Georgia, USA. Bypassing any concentration step, low volumes (280 µl) of influent wastewater were extracted using a commercial kit, and immediately analyzed by RT-qPCR for the SARS-CoV-2 N1 and N2 gene targets. SARS-CoV-2 viral RNA was detected in 76% (193/254) of influent samples, and the recovery of the surrogate bovine coronavirus was 42% (IQR: 28%, 59%). N1 and N2 assay positivity, viral concentration, and flow-adjusted daily viral load correlated significantly with per-capita case reports of COVID-19 at the county-level (ρ = 0.69-0.82). To compensate for the method's high limit of detection (approximately 106-107 copies l-1 in wastewater), we extracted multiple small-volume replicates of each wastewater sample. With this approach, we detected as few as five cases of COVID-19 per 100 000 individuals. These results indicate that a direct-extraction-based workflow for SARS-CoV-2 wastewater surveillance can provide informative and actionable results.

Shaping the Structure and Response of Surface-Grafted Polymer Brushes via the Molecular Weight Distribution.

Breadth in the molecular weight distribution is an inherent feature of synthetic polymer systems. While in the past this was typically considered as an unavoidable consequence of polymer synthesis, multiple recent studies have shown that tailoring the molecular weight distribution can alter the properties of polymer brushes grafted to surfaces. In this Perspective, we describe recent advances in synthetic methods to control the molecular weight distribution of surface-grafted polymers and highlight studies that reveal how shaping this distribution can generate novel or enhanced functionality in these materials.

Fouling Resistance and Release Properties of Poly(sulfobetaine) Brushes with Varying Alkyl Chain Spacer Lengths and Molecular Weights.

We examined the effects of alkyl carbon spacer length (CSL) and molecular weight on fouling resistance and release properties of zwitterionic poly(sulfobetaine methacrylate) brushes. Using surface-initiated atom transfer radical polymerization, we synthesized two series of brushes with CSL = 3 and 4 and molecular weight from 19 to 1500 kg ·mol-1, corresponding to dry brush thickness from around 6 to 180 nm. The brush with CSL = 3 was nearly completely wet with water (independent of molecular weight), whereas the brush with CSL = 4 exhibited a strong increase in water contact angle with molecular weight. Though the two-brush series had distinct wetting properties, both series of brushes exhibited similarly great resistance against fouling by Staphylococcus epidermidis bacteria and Aspergillus niger fungi spores when submerged in water, indicating that neither molecular weight nor CSL strongly affected the antifouling behavior. We also compared the efficacy of brushes against fouling by fungi and silicon oil in air. Brushes grafted to filter paper were strongly fouled by fungi and silicon oil in air. Grafting the polymers to the filter paper, however, greatly enhanced removal of the foulant upon rinsing. The removal of fungi and silicon oil when rinsed with a salt solution was enhanced by 219 and 175%, respectively, as compared to a blank filter paper control. Thus, our results indicate that these zwitterionic brushes can promote foulant removal for dry applications in addition to their well-known fouling resistance in submerged conditions.

Implementation of an antimicrobial stewardship program in the Australian private hospital system: qualitative study of attitudes to antimicrobial resistance and antimicrobial stewardship.

BACKGROUND: Antimicrobial Stewardship (AMS) is a key method to tackle antimicrobial resistance (AMR). In Australia, private hospitals have a higher rate of inappropriate prescribing and non-compliance with antimicrobial guidelines, yet this phenomenon is poorly described. Private hospitals make up 49% of hospitals in Australia, making it vital to understand AMS in this setting. METHODS: This study aimed to explore capabilities, opportunities and motivations for AMR and AMS with stakeholders at an Australian private hospital, and identify barriers and enablers 5 years post-implementation of an AMS program comparing with pre-implementation findings. A mixed-methods study was performed, involving three focus groups with stakeholders. All doctors, nurses and pharmacists at the hospital were invited to complete a survey on their experiences with and awareness of AMR, AMS and antimicrobial prescribing. RESULTS: Thirteen staff took part in the focus groups, 100 staff responded to the survey. Staff understood the importance of the AMS program, but active engagement was low. Staff felt more thorough feedback and monitoring could improve prescribing behaviour, but acknowledged difficulty in private hospitals in changing habits of staff who valued autonomy in making prescribing decisions. Half of respondents felt the current AMS restrictions should continue. Executive engagement may be needed to drive system changes across a complex network. CONCLUSION: AMS awareness increased post-implementation, but staff remained sceptical of its benefits. Engagement and education of medical consultants regarding local benefits of AMS must improve. Enhanced understanding of feedback provision, methods for engagement, and advocacy from leadership will ensure success and longevity for the program.

Barriers and facilitators to technology transfer of NIDILRR grantees.

PURPOSE: The objectives of this mixed-methods study were to gather survey and interview data about the barriers and facilitators from grantees funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) and to extract themes that could inform program changes that would increase technology translation (TT) success in assistive technology (AT). MATERIALS AND METHODS: We developed a TT Barriers and Facilitators survey consisting of Likert scale and multiple-choice questions about barriers and facilitators to TT. With survey respondents who were willing, we conducting a semi-structured interview and asked pointed questions to expand upon survey response rankings and perceived barriers and facilitators. The questions were framed to explore the grantee's personal experience with ATTT and what helped and hindered their individualised processes. RESULTS: Across survey and interview respondents, the three most common themes when exploring the barriers and facilitators of TT were funding, incentives, and collaboration. CONCLUSIONS: Results indicate that there is a need for increased collaboration and access to additional resources such as funding for pilot grants, support to assess technology marketability, help to navigate regulatory and legal aspects, and assistance in establishing goals to help grantees successfully transfer assistive technologies to consumers. IMPLICATIONS FOR REHABILITATIONA large amount of research and development into assistive technology does not lead to tech transfer which means that these technologies are not getting to the people that need them.Educating tech transfer offices at universities about how to transfer AT would improve outcomes greatly.Creating a community of practice where grantees can find academic or industry partners would also increase the likelihood of tech transfer.Some tools to catalyse these improvements are: mentoring, access to consultants, podcasts, and online training.

Effect of Dispersity on the Conformation of Spherical Polymer Brushes.

We show that dispersity (D̵) markedly alters the conformation of spherical polymer brushes. The average lengths (lb) of poly(tert-butyl acrylate) (PtBA) brushes of varying D̵ grafted to nanoparticles were measured using dynamic light scattering. In the semidilute polymer brush (SDPB) regime, the lb of PtBA and polymers from earlier studies of various D̵ could be cleanly collapsed onto a master curve as a function of the scaling variable Nwσ1/3, where Nw is the weight-average degree of polymerization and σ is the grafting density. In the concentrated polymer brush (CPB) regime, however, lb collapsed onto a bifurcated curve as a function of the scaling variable Nwσ1/2, indicating D̵ more strongly affects the average length of brushes with low Nwσ1/2. We propose that the stretching of the stem near the particle surface due to interchain interactions in the CPB regime leads to greater lb in broad dispersity brushes of low but not high Nwσ1/2.

Trace Elements' Contamination of Pediatric Parenteral Nutrition Solutions in Canada: A Cause for Concern.

BACKGROUND: Trace elements' (TEs) contamination of parenteral nutrition (PN) solutions is an ongoing concern. The aims of this study were 1) to measure actual TE concentrations in PN admixtures compared with ordered concentrations and 2) compare TE intake with current recommendations. METHODS: PN admixtures from discarded bags were collected from patients receiving home PN and on inpatient wards. Samples were collected from 72 patients (39 inpatients, 33 receiving home PN). Age, percentage energy intake from PN, and PN orders were collected from patients' charts. PN samples were analyzed for TEs, including chromium (Cr) and manganese (Mn), and concentration measurements compared with ordered concentrations and current recommendations. RESULTS: Measured Cr and Mn concentrations were higher than ordered concentrations: 5.3 ± 1.7 vs 2.8 ± 1.5 µg/L; P < 0.0001 and 11.9 ± 5.9 vs 0.00 µg/L; P < 0.0001, respectively. Chromium contamination alone accounted for over 100% of current recommendations for patients 0-12 months and between 63% and 92% for children >1 year. Contamination of Mn provided all the measured Mn in PN admixtures, since Mn is excluded from PN orders at our institution. Between 70% and 120% of current Mn recommendations were met from contamination. CONCLUSIONS: Cr should be excluded from PN admixtures for children 0-12 months and only one-fourth the current recommendation should be added for pediatric patients >1 year. Manganese should also be excluded from PN admixture for pediatric patients but plasms monitoring 2-3 times per year is recommended for those on long-term PN.

Hydrolysis and Solvolysis as Benign Routes for the End-of-Life Management of Thermoset Polymer Waste.

The production of thermoset polymers is increasing globally owing to their advantageous properties, particularly when applied as composite materials. Though these materials are traditionally used in more durable, longer-lasting applications, ultimately, they become waste at the end of their usable lifetimes. Current recycling practices are not applicable to traditional thermoset waste, owing to their network structures and lack of processability. Recently, researchers have been developing thermoset polymers with the right functionalities to be chemically degraded under relatively benign conditions postuse, providing a route to future management of thermoset waste. This review presents thermosets containing hydrolytically or solvolytically cleavable bonds, such as esters and acetals. Hydrolysis and solvolysis mechanisms are discussed, and various factors that influence the degradation rates are examined. Degradable thermosets with impressive mechanical, thermal, and adhesion behavior are discussed, illustrating that the design of material end-of-life need not limit material performance.

How Can Law and Policy Advance Quality in Genomic Analysis and Interpretation for Clinical Care?

Delivering high quality genomics-informed care to patients requires accurate test results whose clinical implications are understood. While other actors, including state agencies, professional organizations, and clinicians, are involved, this article focuses on the extent to which the federal agencies that play the most prominent roles - the Centers for Medicare and Medicaid Services enforcing CLIA and the FDA - effectively ensure that these elements are met and concludes by suggesting possible ways to improve their oversight of genomic testing.

Patterns of triclosan resistance in Vibrionaceae.

The antimicrobial additive triclosan has been used in personal care products widely across the globe for decades. Triclosan resistance has been noted among Vibrio spp., but reports have been anecdotal and the extent of phenotypic triclosan resistance across the Vibrionaceae family has not been established. Here, triclosan resistance was determined for Vibrionaceae strains across nine distinct clades. Minimum inhibitory concentrations (MIC) were determined for 70 isolates from clinical (n = 6) and environmental sources (n = 64); only two were susceptible to triclosan. The mean MIC for all resistant Vibrionaceae was 53 µg mL-1 (range 3.1-550 µg mL-1), but was significantly different between clades (p < 0.001). The highest mean triclosan MIC was observed in the Splendidus clade (200 µg mL-1; n = 3). Triclosan mean MICs were 68.8 µg mL-1 in the Damselae clade and 45.3 µg mL-1 in the Harveyi clade. The lowest mean MIC was observed in the Cholerae clade with 14.4 µg mL-1, which was primarily represented by clinical strains. There were no significant differences in triclosan MIC among individual species or among environmental strains isolated from different locations. Overall, phenotypic triclosan resistance appears to be widespread across multiple clades of Vibrionaceae.

Tuning Bacterial Attachment and Detachment via the Thickness and Dispersity of a pH-Responsive Polymer Brush.

We investigated the effect of two brush parameters, thickness and dispersity in the molecular weight distribution, on the adhesion of bacteria to pH-responsive poly(acrylic acid) (PAA) brushes synthesized using surface-initiated atom transfer radical polymerization. The attachment and detachment of Staphylococcus epidermidis to PAA brushes at pH 4 and pH 9, respectively, were examined with confocal microscopy. An optimal range of brush thickness, 13-18 nm, was identified for minimizing bacterial adhesion on PAA brushes at pH 4, and bacterial attachment did not depend on the brush dispersity. Increasing either the brush thickness or dispersity detached bacteria from the brushes when the pH was increased from 4 to 9. Bacterial detachment likely arose from an enhanced actuation effect in thick or high-dispersity brushes, as PAA brushes change conformation from collapsed to extended states when the pH is increased from 4 to 9. These results suggest that manipulating the molecular weight distribution provides a route to separately tune the attachment and detachment of bacteria.