Copper and nanostructured anatase rutile and carbon coatings induce adaptive antibiotic resistance.

Contaminated surfaces are vehicles for the spread of infectious disease-causing microorganisms. A strategy to prevent their spread is applying antimicrobial coatings to surfaces. Both nanostructured anatase rutile and carbon (NsARC), a TiO2 formulation, and copper are examples of antimicrobial agents that are used in making or coating door handles and similar surfaces, to reduce microbial loads. Antimicrobial surfaces have been extensively tested for antimicrobial activity but not sublethal effects, such as exposure-associated multiple antibiotic resistance phenotypes usually caused by induction of efflux pump genes. The possibility of NsARC and copper inducing indicative efflux pump pathways was investigated by monitoring the expression of mScarlet fluorescent protein (FP) in two reporter strains of Escherichia coli. There was an increase in the expression of FP in the reporter strains exposed to NsARC and copper relative to the inert control composed of stainless steel. Furthermore we tested E. coli and Staphylococcus aureus following 8 h of exposure to NsARC for changes in resistance to selected antibiotics. E. coli that were exposed to NsARC became more susceptible to kanamycin but there was no significant change in susceptibility of S. aureus to any tested antibiotics. These findings suggests that even though NsARC and copper are antimicrobial, they also have some potential to cause unintended phenotypes.

Identification of ClpP Dual Isoform Disruption as an Antisporulation Strategy for Clostridioides difficile.

The Gram-positive bacterium Clostridioides difficile is a primary cause of hospital-acquired diarrhea, threatening both immunocompromised and healthy individuals. An important aspect of defining mechanisms that drive C. difficile persistence and virulence relies on developing a more complete understanding of sporulation. C. difficile sporulation is the single determinant of transmission and complicates treatment and prevention due to the chemical and physical resilience of spores. By extension, the identification of druggable targets that significantly attenuate sporulation would have a significant impact on thwarting C. difficile infection. By use of a new CRISPR-Cas9 nickase genome editing methodology, stop codons were inserted early in the coding sequence for clpP1 and clpP2 to generate C. difficile mutants that no longer produced the corresponding isoforms of caseinolytic protease P (ClpP). The data show that genetic ablation of ClpP isoforms leads to altered sporulation phenotypes with the clpP1/clpP2 double mutant exhibiting asporogenic behavior. A small screen of known ClpP inhibitors in a fluorescence-based biochemical assay identified bortezomib as an inhibitor of C. difficile ClpP that produces dose-dependent inhibition of purified ClpP. Incubation of C. difficile cultures in the presence of bortezomib reveals antisporulation effects approaching that observed in the clpP1/clpP2 double mutant. This work identifies ClpP as a key contributor to C. difficile sporulation and provides compelling support for the pursuit of small-molecule ClpP inhibitors as C. difficile antisporulating agents. IMPORTANCE Due to diverse roles of ClpP and the reliance of pathogens upon this system for infection, it has emerged as a target for antimicrobial development. Biology regulated by ClpP is organism dependent and has not been defined in Clostridioides difficile. This work identifies ClpP as a key contributor to C. difficile sporulation and provides compelling support for the pursuit of small-molecule ClpP inhibitors as antisporulating agents. The identification of new approaches and/or drug targets that reduce C. difficile sporulation would be transformative and are expected to find high utility in prophylaxis, transmission attenuation, and relapse prevention. Discovery of the ClpP system as a major driver to sporulation also provides a new avenue of inquiry for advancing the understanding of sporulation.

"We can't just have a casual conversation": An institutional ethnography-informed study of work in labour and birth.

Labour and delivery units often become contested workplaces with tensions between obstetrics, nursing, and midwifery practices. These tensions can impede communication and raise concerns about provider wellness and patient safety. Remedying such tensions requires inquiry into the drivers of recurrent problems in interprofessional practice. We engaged in change-oriented inquiry informed by institutional ethnography (IE) within an academic hospital in Toronto, Canada (2017-2019). Clinicians identified critical incident analysis reports used to document recurrent issues for transfers of care (TOC) and consultations between professionals. We then mapped the everyday/everynight work of midwives, nurses, and obstetricians by observing (75 h) and interviewing them (n = 15). We also traced work processes to local (forms and hospital policies) and external (national policies and evidence-based guidelines) texts. Our IE-informed analysis made visible the otherwise hidden links between the everyday work of practitioners and its social organization. Three intrapartum work processes involving midwives consulting with obstetricians were identified: induction of labour with TOC back to midwife once labour was "active", consultation without TOC, and TOC for various indications. Three points of disjuncture complicated these processes: (i) a local "3 consult rule", linked to medico-legal governance and remuneration structures; (ii) subjective interpretations of the "4-cm dilation rule", a policy meant to standardize practice; and (iii) regulations delaying the timing of consultations. The Electronic Fetal Monitoring system served as a powerful text, materializing issues of professional scope and autonomy for midwives, and medicolegal accountability for obstetricians. Our study extends extant evidence that medicine-driven governance of midwifery practices can perpetuate interprofessional challenges. While practitioners spoke of the three disjunctures as 'laws', most also viewed them as ostensibly modifiable. Interprofessional tensions may be addressed by considering how social organization, materialized in texts detailing medico-legal liability and remuneration, can constrain possible practices through regulatory protocols, local ruling policies, and cultural expectations (e.g., documentation practices).

Antimicrobial and biofilm-disrupting nanostructured TiO2 coating demonstrating photoactivity and dark activity.

Antimicrobial materials are tools used to reduce the transmission of infectious microorganisms. Photo-illuminated titania (TiO2) is a known antimicrobial material. Used as a coating on door handles and similar surfaces, it may reduce viability and colonization by pathogens and limit their spread. We tested the survival of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Saccharomyces cerevisiae on a nano-structured TiO2-based thin film, called 'NsARC', and on stainless steel under a variety of light wavelengths and intensities. There was significantly less survival (P <0.001) of all the organisms tested on NsARC compared to inert uncoated stainless steel under all conditions. NsARC was active in the dark and possible mechanisms for this are suggested. NsARC inhibited biofilm formation as confirmed by scanning electron microscopy. These results suggest that NsARC can be used as a self-cleaning and self-sterilizing antimicrobial surface coating for the prevention and reduction in the spread of potentially infectious microbes.

The Infant Cuddler Study: Evaluating the effectiveness of volunteer cuddling in infants with neonatal abstinence syndrome.

OBJECTIVES: St. Michael's Hospital launched a volunteer cuddling program for all infants admitted into the neonatal intensive care unit in October 2015. The program utilizes trained volunteers to cuddle infants when caregivers are not available. This was a pilot study to assess the impact of a volunteer cuddle program on length of stay (LOS) and feasibility of implementation of the program. METHODS: A mixed methods approach was utilized to measure both quantitative and qualitative impact. A pilot cohort study with a retrospective control group assessed the feasibility of implementing a volunteer cuddling program for infants with neonatal abstinence syndrome (NAS). Length of stay was used as a surrogate marker to measure the impact of cuddling on infants being treated for Neonatal Abstinence Syndrome. Focus groups using semi-structured interviews were conducted with volunteers and nurses at the end of the pilot study. RESULTS: LOS was reduced by 6.36 days (U=34, P=0.072) for infants with NAS in the volunteer cuddling program. Focus groups with both bedside nurses and program volunteers described a positive impact of cuddling programs on infants, families, staff, and volunteers alike. CONCLUSIONS: The study results suggest that the volunteer cuddling program may reduce LOS in infants with NAS and have potential economic savings on hospital resources. However, larger prospective cohort studies are needed to confirm these results.

Process-Induced Nanostructures on Anatase Single Crystals via Pulsed-Pressure MOCVD.

The recent global pandemic of COVID-19 highlights the urgent need for practical applications of anti-microbial coatings on touch-surfaces. Nanostructured TiO2 is a promising candidate for the passive reduction of transmission when applied to handles, push-plates and switches in hospitals. Here we report control of the nanostructure dimension of the mille-feuille crystal plates in anatase columnar crystals as a function of the coating thickness. This nanoplate thickness is key to achieving the large aspect ratio of surface area to migration path length. TiO2 solid coatings were prepared by pulsed-pressure metalorganic chemical vapor deposition (pp-MOCVD) under the same deposition temperature and mass flux, with thickness ranging from 1.3-16 mm, by varying the number of precursor pulses. SEM and STEM were used to measure the mille-feuille plate width which is believed to be a key functional nano-dimension for photocatalytic activity. Competitive growth produces a larger columnar crystal diameter with thickness. The question is if the nano-dimension also increases with columnar crystal size. We report that the nano-dimension increases with the film thickness, ranging from 17-42 nm. The results of this study can be used to design a coating which has co-optimized thickness for durability and nano-dimension for enhanced photocatalytic properties.

Nanostructured TiO2 anatase-rutile-carbon solid coating with visible light antimicrobial activity.

TiO2 photocatalyst is of interest for antimicrobial coatings on hospital touch-surfaces. Recent research has focused on visible spectrum enhancement of photocatalytic activity. Here, we report TiO2 with a high degree of nanostructure, deposited on stainless steel as a solid layer more than 10 µm thick by pulsed-pressure-MOCVD. The TiO2 coating exhibits a rarely-reported microstructure comprising anatase and rutile in a composite with amorphous carbon. Columnar anatase single crystals are segmented into 15-20 nm thick plates, resulting in a mille-feuilles nanostructure. Polycrystalline rutile columns exhibit dendrite generation resembling pine tree strobili. We propose that high growth rate and co-deposition of carbon contribute to formation of the unique nanostructures. High vapor flux produces step-edge instabilities in the TiO2, and solid carbon preferentially co-deposits on certain high energy facets. The equivalent effective surface area of the nanostructured coating is estimated to be 100 times higher than standard TiO2 coatings and powders. The coatings prepared on stainless steel showed greater than 3-log reduction in viable E coli after 4 hours visible light exposure. The pp-MOCVD approach could represent an up-scalable manufacturing route for supported catalysts of functional nanostructured materials without having to make nanoparticles.

An Oncology NP-MD Partnership: Challenges and Rewards.

The State of Cancer Care in America report shines a spotlight on the significant increase of cancer survivors by 2026. One strategy to help care for the increased number of patients that require ongoing care is to hire more advanced practice providers. This article provides some keys to developing a positive, professional partnership with oncologists.

O-MAX chemotherapy: high activity in metastatic esophagogastric adenocarcinoma and possible relation to subclinical hemolysis.

OBJECTIVES: Our objectives were to confirm the activity of O-MAX chemotherapy in adenocarcinoma of the stomach and esophagus, particularly the high rate of complete remission (CR) and the relation of subclinical hemolysis to CR. PATIENTS AND METHODS: Twenty-five patients with metastatic esophagogastric adenocarcinoma were treated with O-MAX. Two developed cancer-related hemolytic-uremic syndrome (C-HUS); both achieved CR. Subsequent patients were monitored for serum haptoglobin for subclinical hemolysis. RESULTS: Median survival was 16.5 months. The objective response rate was 90%, with 38% CR. Three patients achieving CR relapsed in the central nervous system and died (2 without systemic disease). Four patients have remained alive, off therapy, the longest for 20 years. Two patients developed clinical C-HUS and 5 of 8 monitored patients developed subclinical hemolysis based on abnormal serum haptoglobin. Four of the patients with subclinical hemolysis achieved CR. Of the 7 patients developing clinical C-HUS or subclinical hemolysis, 6 (86%) achieved CR. CONCLUSIONS: O-MAX appears highly active in esophagogastric adenocarcinoma. A few long-term survivors of metastatic disease are being seen. CR and long-term survival appear to correlate with the development of hemolysis. Although highly promising, these results should be considered only as hypothesis-generating and require confirmation in a prospective trial.

Utility of the neuropsychological evaluation in an acute medical hospital.

Although recent studies have demonstrated the importance of cognitive assessment in medical settings in general, there have been no specific studies addressing the utility of the neuropsychological evaluation in the acute inpatient hospital setting. The current study examined the use of inpatient neuropsychological evaluation by treating physicians in an acute medical hospital for patient care and discharge disposition. Participants were 100 inpatients within an urban medical center who received a neuropsychological evaluation. Results showed 78% of hospital discharge summaries included information regarding the neuropsychological evaluation, 48% referenced specific results, and 68% reported specific recommendations. Further, actual placement outcomes were consistent with the neuropsychological evaluation placement recommendations 80% of the time. The current study supports the utility of neuropsychological evaluations on overall inpatient care, and discusses ways in which the results may be used to communicate the value of neuropsychological services to medical treatment and discharge planning teams, third party payors, and medical center administrators.