Mechanism of Action and Design of Potent Antibacterial Block Copolymer Nanoparticles.

Self-assembled polymer nanoparticles are promising antibacterials, with nonspherical morphologies of particular interest as recent work has demonstrated enhanced antibacterial activity relative to their spherical counterparts. However, the reasons for this enhancement are currently unclear. We have performed a multifaceted analysis of the antibacterial mechanism of action of 1D nanofibers relative to nanospheres by the use of flow cytometry, high-resolution microscopy, and evaluations of the antibacterial activity of pristine and tetracycline-loaded nanoparticles. Low-length dispersity, fluorescent diblock copolymer nanofibers with a crystalline poly(fluorenetrimethylenecarbonate) (PFTMC) core (length = 104 and 472 nm, height = 7 nm, width = 10-13 nm) and a partially protonated poly(dimethylaminoethyl methacrylate) (PDMAEMA) corona (length = 12 nm) were prepared via seeded growth living crystallization-driven self-assembly. Their behavior was compared to that of analogous nanospheres containing an amorphous PFTMC core (diameter of 12 nm). While all nanoparticles were uptaken into Escherichia coli W3110, crystalline-core nanofibers were observed to cause significant bacterial damage. Drug loading studies indicated that while all nanoparticle antibacterial activity was enhanced in combination with tetracycline, the enhancement was especially prominent when small nanoparticles (ca. 15-25 nm) were employed. Therefore, the identified differences in the mechanism of action and the demonstrated consequences for nanoparticle size and morphology control may be exploited for the future design of potent antibacterial agents for overcoming antibacterial resistance. This study also reinforces the requirement of morphological control over polymer nanoparticles for biomedical applications, as differences in activity are observed depending on their size, shape, and core-crystallinity.

Testing specificity and sensitivity of wastewater-based epidemiology for detecting SARS-CoV-2 in four communities on Vancouver Island, Canada.

We report wastewater surveillance of the spread of SARS-CoV-2 based upon 24-h composite influent samples taken weekly from four wastewater treatment plants (WWTP) on Vancouver Island, BC, Canada between January 3, 2021 and July 10, 2021. Samples were analyzed by reverse transcription quantitative polymerase chain reaction targeting the N1 and N2 gene fragments of SARS-CoV-2 and a region of the replication associate protein of the pepper mottle mosaic virus (PMMoV) serving as endemic control. Only a small proportion of samples had quantifiable levels of N1 or N2. Overall case rates are weakly correlated with the concentration (gene copies/L) and with the flux of viral material influent to the WWTP (gene copies/day); the latter accounts for influent flow variations. Poisson multimodal rank correlation accounts for differences between the four WWTP and shows a significant correlation with a significant positive intercept. Receiver operator characteristics (ROC) analysis confirms a cut-off of cases based on amplified/not-amplified experimental data. At the optimal cut point of 19 (N1) or 17 (N2) cases/week/100,000 the sensitivity and specificity is about 75% for N1 and 67% for N2.

Light-Induced Anti-Bacterial Effect Against Staphylococcus aureus of Porphyrin Covalently Bonded to a Polyethylene Terephthalate Surface.

Antimicrobial photodynamic inactivation represents a promising and potentially greener alternative to conventional antimicrobials, and a solution for multidrug-resistant strains. The current study reports the development and characterization of tetra-substituted diazirine porphyrin covalently bonded to polyethylene terephthalate (PET) and its use as an antimicrobial surface. The diazirine moiety on the porphyrin was activated using a temperature of 120 °C, which initiated a C-H insertion mechanism that irreversibly functionalized the PET surface. Activation of the surface with white LED light in phosphate-buffered saline (PBS) led to singlet oxygen generation, which was detected via the degradation of 9,10-anthracenediylbis(methylene)dimalonic acid (ADMA) over time. The bactericidal effect of the 1O2-producing surface against Staphylococcus aureus was determined qualitatively and quantitatively. The growth of the pathogen beneath porphyrin-functionalized PET coupons was reduced; moreover, the PET coupons resulted in a 1.76-log reduction in cell counts after exposure to white LED light for 6 h. This is a promising material and platform for the development of safer antimicrobial surfaces, with applications in healthcare, food packaging, marine surfaces, and other surfaces in the environment.

Presenting cases in front of patients: implications for a key medical education genre.

Case presentations have been researched as both an important form of intra/inter-professional communication, where a patient's clinical information is shared among health professionals involved in their care, and an equally key discursive tool in education, where learners independently assess a patient and present the case to their preceptor and/or care team. But what happens to the case presentation, a genre that governs physician (and learner) talk about patients, when it is used in patients' presence? While they were commonly used at the bedside in the past, case presentations today are more commonly performed in hallways or conference rooms, out of patient earshot. This paper draws on interview data from a study involving patient-present case presentations in a medical education setting. Our analysis asks what participants' metageneric comments about the encounter can teach us about the genre, about patient involvement in medical education, and about linguistic adaptations to the genre that the profession might make to support patient involvement.

Patient-present teaching in the clinic: Effect on agency and professional behaviour.

BACKGROUND/PURPOSE: Although much has been written about the medical learning environment, the patient, who is the focus of care, is rarely the focus in this literature. The purpose of this study was to explore the role of the patient as an active participant with agency in the medical learning environment from the standpoint of the learner, the attending physician, and most importantly, the patient. We hoped to gain insights into the mechanisms that can reinforce professional values such as patient-centred and respectful behaviours in a patient-present learning environment. METHODS: We conducted this study in an ambulatory internal medicine clinic using 'patient-present' clinic visits. All case presentations occurred in examination rooms with the patient. We invited participants (attending physicians, undergraduate and postgraduate learners, patients and family members) to participate in semistructured interviews after each clinic visit to explore the impact of the patient-present learning environment. We recruited 34 participants in the study; 10 attending physicians, 12 learners, 10 patients and 2 family members. We analysed the data deductively using a conceptual framework of agency. SUMMARY/RESULTS: We identified three major insights: (1) Patients felt engaged and valued opportunities to be heard; (2) Attending physicians and learners reported a more respectful learning environment and a positive though challenging teaching and learning experience; and (3) A hidden curriculum emerged in a performance-based view of professional behaviour. CONCLUSIONS: Patient-present teaching engaged patients and enhanced their agency by recasting the patient as the central focus within the healthcare encounter. We identified a tension between performing and learning. This study adds new insights to the concept of patient centredness and professionalism from the perspectives of all participants in the medical teaching and learning environment.

Biofouling detection methods that are widely applicable and useful across disciplines: a mini-review.

Biofouling, or the build-up of microorganisms in a biofilm at the solid-water or water-air interface, is an interdisciplinary problem. Biofouling causes various issues including clogging systems, contaminating devices, and creating infections that are extremely difficult to treat, to name but a few. Therefore, engineers, pharmacologists, microbiologists, wastewater treatment operators, chemists, food preservative formulators, home and personal care product formulators, and toxicologists all play a role in studying and have an interest in solving biofouling. High-throughput studies on biofilm prevention and removal can take the form of biofilm antimicrobial microdilution susceptibility (BAMS) tests. Due to vested interests of many disciplines, the results from these tests should be applicable and useful to each discipline. This critical review analyses the focuses, biological implications, and metrics required by each discipline. The possible detection methods that could satisfy each desired metric are then summarized. The detection methods were analysed in order to recommend two methods of biofilm detection, Crystal Violet stain and the LIVE/DEAD BacLight stain, which correspond with three metrics including total biomass, log reduction, and the MIC, BPC, MBIC, MBC, BBC, and/or MBEC values. Determining these three metrics for each BAMS test will allow this type of research to be widely applicable and useful across many disciplines.

A proposed learning environment framework for virtual care.

The way in which health care is delivered has rapidly changed since the onset of the COVID-19 pandemic, with a rapid increase in virtual delivery of clinical care. As a result, the learning environment (LE) in health professions education, which has traditionally been situated in the bricks-and-mortar clinical context, now also requires attention to the virtual space. As a frequently examined topic in the health professions literature, the LE is a critical component in the development and training of future healthcare professionals. Based on a published conceptual framework for the LE from Gruppen et al. in 2019, a conceptual framework for how the LE can manifest through virtual care space is presented here. The four components of personal, social, organizational, physical/virtual spaces are explored, with a discussion of how they can be integrated into virtual care. The authors provide suggestions that health professions educators can consider when adapting their LE to the virtual environment and highlight aspects of its integration that require further research and investigation.

La prestation des soins de santé a connu un changement fulgurant depuis le début de la pandémie de la COVID-19, notamment en raison de la virtualisation des soins cliniques. Par conséquent, l'environnement d'apprentissage (EA) qui, dans l'enseignement traditionnel des professions de la santé, se situait dans un cadre clinique physique, doit désormais inclure l'espace virtuel. Sujet souvent exploré dans la littérature en sciences de la santé, l'environnement d'apprentissage est un élément essentiel de la formation des futurs professionnels de la santé. Nous proposons un cadre conceptuel, inspiré du cadre de l'EA élaboré par Gruppen et al. en 2019, sur la façon de définir un EA dans l'espace de soins virtuel. Après avoir exploré les quatre dimensions de l'espace, à savoir personnelle, sociale, organisationnelle et physique/virtuelle, les auteurs analysent la façon de les intégrer dans les soins virtuels. Ils formulent des suggestions à l'intention des enseignants des professions de la santé concernant l'adaptation de leur environnement d'apprentissage à l'environnement virtuel, tout en soulignant les aspects d'une telle intégration qui nécessitent des recherches plus approfondies.

The Best-Practice Organism for Single-Species Studies of Antimicrobial Efficacy against Biofilms Is Pseudomonas aeruginosa.

As potable water scarcity increases across the globe; it is imperative to identify energy and cost-effective processes for producing drinking-water from non-traditional sources. One established method is desalination of brackish and seawater via reverse osmosis (RO). However, the buildup of microorganisms at the water-membrane interface, known as biofouling, clogs RO membranes over time, increasing energy requirements and cost. To investigate biofouling mitigation methods, studies tend to focus on single-species biofilms; choice of organism is crucial to producing useful results. To determine a best-practice organism for studying antimicrobial treatment of biofilms, with specific interest in biofouling of RO membranes, we answered the following two questions, each via its own semi-systematic review: 1. Which organisms are commonly used to test antimicrobial efficacy against biofilms on RO membranes? 2. Which organisms are commonly identified via genetic analysis in biofilms on RO membranes? We then critically review the results of two semi-systematic reviews to identify pioneer organisms from the listed species. We focus on pioneer organisms because they initiate biofilm formation, therefore, inhibiting these organisms specifically may limit biofilm formation in the first place. Based on the analysis of the results, we recommend utilizing Pseudomonas aeruginosa for future single-species studies focused on biofilm treatment including, but not limited to, biofouling of RO membranes.

Learning in Faculty Development: The Role of Social Networks.

PURPOSE: Faculty development is increasingly acknowledged as an important aspect of health professions education. Its conceptualization has evolved from an individual skills training activity to contemporary notions that draw on an organizational model. This organizational model recognizes relationships and networks as important mediators of knowledge mobilization. Although such conceptual advancements are critical, we lack empirical evidence and robust insights into how social networks function to shape learning in faculty development. The purpose of this study was to understand how informal professional social networks influence faculty development learning in the health professions. METHOD: This study used a qualitative social network approach to explore how teaching faculty's relationships influenced their learning about teaching. The study was conducted in 2018 in an undergraduate course at a Canadian medical school. Eleven faculty participants were recruited, and 3 methods of data collection were employed: semistructured interviews, participant-drawn sociograms, and demographic questionnaires. RESULTS: The social networks of faculty participants influenced their learning about teaching in the following 4 dimensions: enabling and mobilizing knowledge acquisition, shaping identity formation, expressing vulnerability, and scaffolding learning. CONCLUSIONS: Faculty developers should consider faculty's degree of social embeddedness in their professional social networks, as our study suggests this may influence their learning about teaching. The findings align with recent calls to conceptually reorient faculty development in the health professions as a dynamic social enterprise.

Addressing technical barriers for reliable, safe removal of fluoride from drinking water using minimally processed bauxite ores.

Throughout the developing world, over 200 million people drink groundwater containing fluoride concentrations surpassing the World Health Organization's maximum recommended contaminant level (WHO-MCL) of 1.5 mg F-/L, resulting in adverse health effects ranging from mottled tooth enamel to debilitating skeletal fluorosis. Existing technologies to remove fluoride from water, such as reverse osmosis and filtration with activated alumina, are expensive and are not accessible for low-income communities. Our group and others have demonstrated that minimally-processed bauxite ores can remove fluoride to safe levels at a fraction of the cost of activated alumina. We report results from testing for some technical challenges that may arise in field deployment of this technology at large scale, particularly in a sufficiently robust manner for application in development contexts. Anticipating possible modes of failure and addressing these challenges in advance in the laboratory is particularly important for technologies for vulnerable communities where the opportunity to re-launch pilot projects is limited and small failures can keep solutions from the people that need them most. This work addresses three potential technical barriers to reliable removal of fluoride from drinking water with bauxite ore from Visakhapatnam, Andhra Pradesh, India. We evaluate competition from co-occurring ions, adsorption reversibility, and potability of the product water with regards to leaching of undesirable ions during treatment with various adsorbent materials including raw and thermally activated bauxite, and synthetic gibbsite (a simple model system). Under the conditions tested, the presence of phosphate significantly impacts fluoride adsorption capacity on all adsorbents. Sulfate impacts fluoride adsorption on gibbsite, but not on either bauxite adsorbent. Nitrate and silicate (as silicic acid), tested only with gibbsite, do not affect fluoride adsorption capacity. Both thermally activated bauxite and gibbsite show non-reversible adsorption of fluoride at a pH of 6. Raw bauxite leached arsenic and manganese in a TCLP leaching test at levels indicating the need for ongoing monitoring of treated water, but not precluding safe deployment of bauxite as a fluoride remediation technology. Understanding these phenomena is crucial to ensure field deployment over large diverse geographical areas with aquifers varying in groundwater composition, and for ensuring that the appropriate engineering processes are designed for field implementation of this innovation.

Trace Metal Content of Coal Exacerbates Air-Pollution-Related Health Risks: The Case of Lignite Coal in Kosovo.

More than 6600 coal-fired power plants serve an estimated five billion people globally and contribute 46% of annual CO2 emissions. Gases and particulate matter from coal combustion are harmful to humans and often contain toxic trace metals. The decades-old Kosovo power stations, Europe's largest point source of air pollution, generate 98% of Kosovo's electricity and are due for replacement. Kosovo will rely on investment from external donors to replace these plants. Here, we examine non-CO2 emissions and health impacts by using inductively coupled plasma mass spectrometry (ICP-MS) to analyze trace metal content in lignite coal from Obilic, Kosovo. We find significant trace metal content normalized per kWh of final electricity delivered (As (22.3 ± 1.7), Cr (44.1 ± 3.5), Hg (0.08 ± 0.010), and Ni (19.7 ± 1.7) mg/kWhe). These metals pose health hazards that persist even with improved grid efficiency. We explore the air-pollution-related risk associated with several alternative energy development pathways. Our analysis estimates that Kosovo could avoid 2300 premature deaths by 2030 with investments in energy efficiency and solar PV backed up by natural gas. Energy policy decisions should account for all associated health risks, as should multilateral development banks before guaranteeing loans on new electricity projects.

Synthesis and reactivity of tantalum corrole complexes.

Reaction of the free base corrole (Mes2(p-OMePh)corrole)H3 with tantalum trialkyl precursors TaMe3Cl2 and TaBn3NtBu resulted in the formation of the tantalum dichloride (1) and tantalum imido (4) corrole complexes via alkane elimination. The X-ray crystal structures of these two compounds have been determined and the structural parameters are discussed. The Ta centre of 1 was found to sit out of the plane of the corrole ring by 0.903 Å and is cis-ligated, similarly to what has been reported for group 4 porphyrin complexes. From complex 1 we synthesized the dimethyl derivative (2), the reactivity of which is compared to an analogous tantalum dimethyl porphyrin cation. The imido complex 4 reacted with triphenylmethanol and 4-methylbenzyl alcohol, resulting in different extents of protonation of the imido group.

Recent developments in out-of-plane metallocorrole chemistry across the periodic table.

This article presents a brief review of recent developments in metallocorrole chemistry, with a focus on species with significant displacement of the metal from the N4 plane of the corrole ring. Comparisons based on X-ray crystallographic data are made between a range of early and/or heavy transition metal, lanthanide, actinide, and main group metallocorrole species.

Corroles that "click": modular synthesis of azido- and propargyl-functionalized metallocorrole complexes and convergent synthesis of a bis-corrole scaffold.

Bis-corroles have been prepared through a convergent synthesis using a copper-catalyzed azide-alkyne cycloaddition. Synthesis of the final homo- and heterobimetallic complexes has been achieved in three to four steps from commercially available materials in good overall yield. Meso-substituted corroles functionalized with a single azido or propargyl group were used as key starting materials. (C6F5)2(p-O(CH2CCH)Ph)corroleH3 (1) and ((C6F5)2(m-CH2N3)Ph)corroleH3 (3) were metalated with copper or iron and attached by Huisgen azide-alkyne cycloaddition ("click" reaction) first to small substrates and then to each other, demonstrating a convergent synthesis of bimetallic bis-corrole molecules.

Synthesis, structure and reactivity of group 4 corrole complexes.

A series of early transition metal corrole complexes has been prepared via salt metathesis with the corresponding lithium corrole. Their characterization by single crystal X-ray diffraction, NMR, and absorption spectroscopy is described. Organometallic derivatives of the titanium complex were obtained via treatment of 2 with NaCp* or ClMgCH2SiMe3.