Reducing sickness absence among public-sector healthcare employees: the difference-making roles of managerial and employee participation.

PURPOSE: Evaluations of organizational-level interventions to prevent work-related illness have identified enabling factors, but knowledge of necessary and sufficient conditions for intervention success is needed. The aim was to identify difference-making factors that distinguish intervention groups with and without a positive intervention effect on sickness absence. METHODS: An organizational-level intervention designed to decrease sickness absence by providing support from process facilitators was implemented at eight healthcare workplaces in Sweden between 2017 and 2018. We applied coincidence analysis (CNA) to analyze 34 factors and determine which factors were necessary and sufficient for a successful implementation of tailored interventional measures on an organizational level (dichotomous) and reduced sickness absence (trichotomous). RESULTS: Two factors perfectly explained both the presence and absence of a successful implementation: "a high sense of urgency" and "good anchoring and participation from the strategic management". The presence of either of these factors alone was sufficient for successful implementation, whereas the joint absence of both conditions was necessary and sufficient for the absence of successful implementation and an intervention effect. In addition, high employee participation was both necessary and sufficient for a high intervention effect. For organizations without high employee participation, successful implementation led to a medium-effect size. CONCLUSIONS: This study identified participation as a difference-maker in the implementation process. Participation from different stakeholders turned out to be important in different phases. When implementing organizational-level interventions, high participation from both strategic management and employees appears to be crucial in terms of the intervention's effect on sickness absence.

A global resource allocation strategy governs growth transition kinetics of Escherichia coli.

A grand challenge of systems biology is to predict the kinetic responses of living systems to perturbations starting from the underlying molecular interactions. Changes in the nutrient environment have long been used to study regulation and adaptation phenomena in microorganisms and they remain a topic of active investigation. Although much is known about the molecular interactions that govern the regulation of key metabolic processes in response to applied perturbations, they are insufficiently quantified for predictive bottom-up modelling. Here we develop a top-down approach, expanding the recently established coarse-grained proteome allocation models from steady-state growth into the kinetic regime. Using only qualitative knowledge of the underlying regulatory processes and imposing the condition of flux balance, we derive a quantitative model of bacterial growth transitions that is independent of inaccessible kinetic parameters. The resulting flux-controlled regulation model accurately predicts the time course of gene expression and biomass accumulation in response to carbon upshifts and downshifts (for example, diauxic shifts) without adjustable parameters. As predicted by the model and validated by quantitative proteomics, cells exhibit suboptimal recovery kinetics in response to nutrient shifts owing to a rigid strategy of protein synthesis allocation, which is not directed towards alleviating specific metabolic bottlenecks. Our approach does not rely on kinetic parameters, and therefore points to a theoretical framework for describing a broad range of such kinetic processes without detailed knowledge of the underlying biochemical reactions.

Shifting from an individual to an organizational perspective in work environment management - a process evaluation of a six-year intervention program within the Swedish public sector.

BACKGROUND: Working systematically with the work environment, particularly the organizational and psychosocial work environment entails several challenges for employers. There is a lack of knowledge on how to best undertake this work. Thus, the aim of this study is to evaluate the process of a six-year organizational-level intervention program where workplaces could apply for additional funds to implement preventive intervention measures, with the intention of improving working conditions and reducing sickness absence within the Swedish public sector. METHODS: The program management process was studied using a mixed-method approach combining qualitative document and content analyses based on process documentation produced between 2017 and 2022 (n = 135), interviews with internal occupational health services professionals in 2021 (n = 9) and quantitative descriptive analyses of submitted applications with decisions from 2017 to 2022 (n = 621). RESULTS: Qualitative analyses of the process documentation revealed concerns from the project group regarding access to sufficient competence and resources among stakeholders and participating workplaces, and role conflicts and ambiguities between the program and everyday operations. To address these challenges, the application process was developed over time using the knowledge gained from previous years. A change in the mental models in work environment management, from an individual to an organizational perspective, was seen among the project group and the internal occupational health services responsible for implementing most of the granted intervention measures. In addition, the proportion of granted intervention measures on an organizational level increased throughout the years from 39% in 2017 to 89% in 2022. The changes in the application process were believed to be the main contributor to the change among the applying workplaces. CONCLUSIONS: Results indicate that a long-term organizational-level workplace intervention program may be used, by the employer, as a tool for shifting from an individual- to an organizational perspective in the work environment management. However, additional measures on multiple levels need to be implemented to secure a sustainable shift in perspective within the organization.

Neomorphic DNA-binding enables tumor-specific therapeutic gene expression in fusion-addicted childhood sarcoma.

Chimeric fusion transcription factors are oncogenic hallmarks of several devastating cancer entities including pediatric sarcomas, such as Ewing sarcoma (EwS) and alveolar rhabdomyosarcoma (ARMS). Despite their exquisite specificity, these driver oncogenes have been considered largely undruggable due to their lack of enzymatic activity.Here, we show in the EwS model that - capitalizing on neomorphic DNA-binding preferences - the addiction to the respective fusion transcription factor EWSR1-FLI1 can be leveraged to express therapeutic genes.We genetically engineered a de novo enhancer-based, synthetic and highly potent expression cassette that can elicit EWSR1-FLI1-dependent expression of a therapeutic payload as evidenced by episomal and CRISPR-edited genomic reporter assays. Combining in silico screens and immunohistochemistry, we identified GPR64 as a highly specific cell surface antigen for targeted transduction strategies in EwS. Functional experiments demonstrated that anti-GPR64-pseudotyped lentivirus harboring our expression cassette can specifically transduce EwS cells to promote the expression of viral thymidine kinase sensitizing EwS for treatment to otherwise relatively non-toxic (Val)ganciclovir and leading to strong anti-tumorigenic, but no adverse effects in vivo. Further, we prove that similar vector designs can be applied in PAX3-FOXO1-driven ARMS, and to express immunomodulatory cytokines, such as IL-15 and XCL1, in tumor entities typically considered to be immunologically 'cold'.Collectively, these results generated in pediatric sarcomas indicate that exploiting, rather than suppressing, the neomorphic functions of chimeric transcription factors may open inroads to innovative and personalized therapies, and that our highly versatile approach may be translatable to other cancers addicted to oncogenic transcription factors with unique DNA-binding properties.

Methodological approach for measuring the effects of organisational-level interventions on employee withdrawal behaviour.

BACKGROUND: Theoretical frameworks have recommended organisational-level interventions to decrease employee withdrawal behaviours such as sickness absence and employee turnover. However, evaluation of such interventions has produced inconclusive results. The aim of this study was to investigate if mixed-effects models in combination with time series analysis, process evaluation, and reference group comparisons could be used for evaluating the effects of an organisational-level intervention on employee withdrawal behaviour. METHODS: Monthly data on employee withdrawal behaviours (sickness absence, employee turnover, employment rate, and unpaid leave) were collected for 58 consecutive months (before and after the intervention) for intervention and reference groups. In total, eight intervention groups with a total of 1600 employees participated in the intervention. Process evaluation data were collected by process facilitators from the intervention team. Overall intervention effects were assessed using mixed-effects models with an AR (1) covariance structure for the repeated measurements and time as fixed effect. Intervention effects for each intervention group were assessed using time series analysis. Finally, results were compared descriptively with data from process evaluation and reference groups to disentangle the organisational-level intervention effects from other simultaneous effects. RESULTS: All measures of employee withdrawal behaviour indicated statistically significant time trends and seasonal variability. Applying these methods to an organisational-level intervention resulted in an overall decrease in employee withdrawal behaviour. Meanwhile, the intervention effects varied greatly between intervention groups, highlighting the need to perform analyses at multiple levels to obtain a full understanding. Results also indicated that possible delayed intervention effects must be considered and that data from process evaluation and reference group comparisons were vital for disentangling the intervention effects from other simultaneous effects. CONCLUSIONS: When analysing the effects of an intervention, time trends, seasonal variability, and other changes in the work environment must be considered. The use of mixed-effects models in combination with time series analysis, process evaluation, and reference groups is a promising way to improve the evaluation of organisational-level interventions that can easily be adopted by others.

High-affinity CD16-polymorphism and Fc-engineered antibodies enable activity of CD16-chimeric antigen receptor-modified T cells for cancer therapy.

BACKGROUND: CD16-chimeric antigen receptors (CAR) T cells recognise the Fc-portion of therapeutic antibodies, which can enable the selective targeting of different antigens. Limited evidence exists as to which CD16-CAR design and antibody partner might be most effective. We have hypothesised that the use of high-affinity CD16 variants, with increased Fc-terminus antibody affinity, combined with Fc-engineered antibodies, would provide superior CD16-CAR T cell efficacy. METHODS: CD16-CAR T (wild-type or variants) cells were co-cultured with Panc-1 pancreatic cancer, Raji lymphoma or A375 melanoma cells in the presence or absence of anti-CD20, anti-MCSP, wild-type or the glycoengineered antibody variants. The endpoints were proliferation, activation, and cytotoxicity in vitro. RESULTS: The CD16 158 V variant of CD16-CAR T cells showed increased cytotoxic activity against all the tested cancer cells in the presence of the wild-type antibody directed against MCSP or CD20. Glycoengineered antibodies enhanced CD16-CAR T cell activity irrespective of CD16 polymorphisms as compared with the wild-type antibody. The combination of the glycoengineered antibodies with the CD16-CAR 158 V variant synergised as seen by the increase in all endpoints. CONCLUSION: These results indicate that CD16-CAR with the high-affinity CD16 variant 158 V, combined with Fc-engineered antibodies, have high anti-tumour efficacy.

Velocity-specific and time-dependent adaptations following a standardized Nordic Hamstring Exercise training.

The Nordic Hamstring Exercise (NHE) is effective for selective hamstring strengthening to improve muscle balance between knee flexors and extensors. The purpose of this study (within subject design of repeated measures) was to determine the effects of a standardized 4-week NHE training on thigh strength and muscle balance with concomitant kinetic and kinematic monitoring. Sixteen male sprinters (22 years, 181 cm, 76 kg) performed a standardized 4-week NHE training consisting of three sessions per week (each 3×3 repetitions). Six rope-assisted and six unassisted sessions were performed targeting at a constant knee extension angular velocity of ~15°/s across a ~90-100° knee joint range of motion. Kinetic (peak and mean moment, impulse) and kinematic parameters (eg, ROM to downward acceleration, ROMDWA ) were recorded during selected sessions. Unilateral isokinetic tests of concentric and eccentric knee flexors and extensors quantified muscle group-, contraction mode-, and velocity-specific training adaptations. Peak moments and contractional work demonstrated strong interactions of time with muscle group, contraction modes, and angular velocities (η²>.150). NHE training increased eccentric hamstring strength by 6%-14% as well as thigh muscle balance with biggest adaptations at 150°/s 2 weeks after NHE training. Throughout the training period significant increases (P<.001) of peak (η²=.828) and mean moments (η²=.611) became apparent, whereas the impulse and the ROMDWA of unassisted NHE repetitions remained unchanged (P>.05). A 4-week NHE training significantly strengthened the hamstrings and improved muscle balance between knee flexors and extensors. Despite the slow training velocity, biggest adaptations emerged at the highest velocity 2 weeks after training ended.

Stimuli-Responsive Codelivery of Oligonucleotides and Drugs by Self-Assembled Peptide Nanoparticles.

Ever more emerging combined treatments exploiting synergistic effects of drug combinations demand smart, responsive codelivery carriers to reveal their full potential. In this study, a multifunctional stimuli-responsive amphiphilic peptide was designed and synthesized to self-assemble into nanoparticles capable of co-bearing and -releasing hydrophobic drugs and antisense oligonucleotides for combined therapies. The rational design was based on a hydrophobic l-tryptophan-d-leucine repeating unit derived from a truncated sequence of gramicidin A (gT), to entrap hydrophobic cargo, which is combined with a hydrophilic moiety of histidines to provide electrostatic affinity to nucleotides. Stimuli-responsiveness was implemented by linking the hydrophobic and hydrophilic sequence through an artificial amino acid bearing a disulfide functional group (H3SSgT). Stimuli-responsive peptides self-assembled in spherical nanoparticles in sizes (100-200 nm) generally considered as preferable for drug delivery applications. Responsive peptide nanoparticles revealed notable nucleotide condensing abilities while maintaining the ability to load hydrophobic cargo. The disulfide cleavage site introduced in the peptide sequence induced responsiveness to physiological concentrations of reducing agent, serving to release the incorporated molecules. Furthermore, the peptide nanoparticles, singly loaded or coloaded with boron-dipyrromethene (BODIPY) and/or antisense oligonucleotides, were efficiently taken up by cells. Such amphiphilic peptides that led to noncytotoxic, reduction-responsive nanoparticles capable of codelivering hydrophobic and nucleic acid payloads simultaneously provide potential toward combined treatment strategies to exploit synergistic effects.

A search strategy for detecting duodenoscope-associated infections: a retrospective observational study.

BACKGROUND: Duodenoscope-associated infections (DAIs) are exogenous infections resulting from the use of contaminated duodenoscopes. Though numerous outbreaks of DAI have involved multidrug-resistant micro-organisms (MDROs), outbreaks involving non-MDROs are also likely to occur. Detection challenges arise as these infections often resolve before culture or because causative strains are not retained for comparison with duodenoscope strains. AIM: To identify and analyse DAIs spanning a seven-year period in a tertiary care medical centre. METHODS: This was a retrospective observational study. Duodenoscope cultures positive for gastrointestinal flora between March 2015 and September 2022 were paired with duodenoscope usage data to identify patients exposed to contaminated duodenoscopes. Analysis encompassed patients treated after a positive duodenoscope culture and those treated within the interval from a negative to a positive culture. Patient identification numbers were cross-referenced with a clinical culture database to identify patients developing infections with matching micro-organisms within one year of their procedure. A 'pair' was established upon a species-level match between duodenoscope and patient cultures. Pairs were further analysed via antibiogram comparison, and by whole-genome sequencing (WGS) to determine genetic relatedness. FINDINGS: Sixty-eight pairs were identified; of these, 21 exhibited matching antibiograms which underwent WGS, uncovering two genetically closely related pairs categorized as DAIs. Infection onset occurred up to two months post procedure. Both causative agents were non-MDROs. CONCLUSION: This study provides crucial insights into DAIs caused by non-MDROs and it highlights the challenge of DAI recognition in daily practice. Importantly, the delayed manifestation of the described DAIs suggests a current underestimation of DAI risk.

Active follow-up of patients identified with multidrug-resistant Gram-negative bacteria to discontinue contact precautions and isolation measures.

BACKGROUND: It is essential to refrain from unnecessary isolation measures indicated for patients identified with multidrug-resistant Gram-negative bacteria (MDR-GNB). AIM: To evaluate whether a pro-active follow-up strategy to discontinue isolation measures of patients identified with MDR-GNB (without carbapenemase production) resulted in reduced isolation days during hospitalization, compared to passive follow-up. METHODS: A comparison was made between active and passive follow-up strategies over a two-year period after first MDR-GNB identification. Patients could be declared negative after two consecutive negative screening cultures. Active follow-up patients received a questionnaire for screening cultures within six months of MDR-GNB identification. Of the 2208 patients included, 1424 patients (64.5%) underwent passive follow-up and 784 patients (35.5%) underwent active follow-up. FINDINGS: A significantly higher proportion of active follow-up patients who had sufficient (at least two) screening cultures were declared MDR-GNB negative compared to those with passive follow-up; 66.9% vs 20.6% (P < 0.001) for adult patients and 76.0% vs 17.1% (P < 0.001) for paediatric patients. A comparison between active follow-up patients with sufficient versus those with active follow-up but insufficient cultures revealed a reduction of isolation days for paediatric patients (median 10.6 vs 1.6 days; P = 0.031). Though this difference was not statistically significant for adults (median 5.3 vs 4.2 isolation days), there was a valuable decrease in the number of isolation days for both adult and paediatric patients under active follow-up with sufficient (≥2) cultures, indicating clinical relevance. CONCLUSION: We recommend an active follow-up strategy for patients identified with an MDR-GNB, to prevent further unneeded infection prevention measures.

Proposal for a screening protocol for Candida auris colonization.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast which can cause severe infection in hospitalized patients. Since its first detection in 2009, C. auris has spread globally. The control and elimination of this pathogen in a hospital setting is particularly challenging because of its ability to form biofilms, allowing for long-term patient colonization and persistence in the environment. Identification of C. auris from cultures is difficult due to the morphologic similarities to other yeasts, its slow growth, and the low culture sensitivity when using standard agars and temperatures. AIM: We have developed a screening protocol for C. auris colonization using an in-house-developed polymerase chain reaction (PCR), combined with confirmatory culture in optimized conditions. METHODS: C. auris-specific primers and probe were developed, targeting the internal transcribed spacer (ITS) region, and specificity was confirmed in silico using the BLAST tool. The PCR was validated using a panel of 12 C. auris isolates and 103 isolates from 22 other Candida species and was shown to be 100% accurate. The limit of detection of the assay was determined at approximately four cells per PCR. FINDINGS: C. auris screening was introduced on February 15th, 2023, and was used for patients who had been admitted to a healthcare facility abroad in the two months prior to admission to our hospital. The screening protocol included swabs from nose, throat, rectum, axilla, and groin. In the first eight months, 199 patients were screened and seven were found positive (4%). CONCLUSION: Our proposed screening protocol may contribute to control C. auris in hospitals.

Regional variation in the interpretation of contact precautions for multi-drug-resistant Gram-negative bacteria: a cross-sectional survey.

BACKGROUND: Contact precautions are recommended when caring for patients with carbapenemase-producing Enterobacterales (CPE), carbapenemase-producing Pseudomonas aeruginosa (CPPA), and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E). AIM: Our aim was to determine the interpretation of contact precautions and associated infection prevention and control (IPC) measures in the non-ICU hospital setting for patients with CPE, CPPA or ESBL-E in 11 hospitals in the Southwest of the Netherlands. METHODS: A cross-sectional survey was developed to collect information on all implemented IPC measures, including use of personal protective equipment, IPC measures for visitors, cleaning and disinfection, precautions during outpatient care and follow-up strategies. All 11 hospitals were invited to participate between November 2020 and April 2021. FINDINGS: The survey was filled together with each hospital. All hospitals installed isolation precautions for patients with CPE and CPPA during inpatient care and day admissions, whereas 10 hospitals (90.9%) applied isolation precautions for patients with ESBL-E. Gloves and gowns were always used during physical contact with the patient in isolation. Large variations were identified in IPC measures for visitors, cleaning and disinfection products used, and precautions during outpatient care. Four hospitals (36.4%) actively followed up on CPE or CPPA patients with the aim of declaring them CPE- or CPPA-negative as timely as possible, and two hospitals (20.0%) actively followed up on ESBL-E patients. CONCLUSION: Contact precautions are interpreted differently between hospitals, leading to regional differences in IPC measures applied in clinical settings. Harmonizing infection-control policies between the hospitals could facilitate patient transfers and benefit collective efforts of preventing transmission of multi-drug-resistant Gram-negative bacteria.

Good performance of the SpectraCellRA system for typing of methicillin-resistant Staphylococcus aureus isolates.

Typing of methicillin-resistant Staphylococcus aureus (MRSA) remains necessary in order to assess whether transmission of MRSA occurred and to what extent infection prevention measures need to be taken. Raman spectroscopy (SpectraCellRA [SCRA]; RiverD International, Rotterdam, The Netherlands) is a recently developed tool for bacterial typing. In this study, the performance (typeability, discriminatory power, reproducibility, workflow, and costs) of the SCRA system was evaluated for typing of MRSA strains isolated from patients and patients' household members who were infected with or colonized by MRSA. We analyzed a well-documented collection of 113 MRSA strains collected from 54 households. The epidemiological relationship between the MRSA strains within one household was used as the gold standard. Pulsed-field gel electrophoresis (PFGE) was used for discrepancy analysis. The results of SCRA analysis on the strain level corresponded with epidemiological data for 108 of 113 strains, a concordance of 95.6%. When analyzed at the household level, the results of SCRA were correct for 49 out of 54 households, a concordance of 90.7%. Concordance on the strain level with epidemiological data for PFGE was 93.6% (103/110 isolates typed). Concordance on the household level with epidemiological data for PFGE was 93.5% (49/53 households analyzed). With PFGE regarded as the reference standard, the conclusions reached with Raman spectroscopy were identical to those reached with PFGE in 100 of 105 cases (95.2%). The reproducibility of SCRA was found to be 100%. We conclude that the SpectraCellRA system is a fast, easy-to-use, and highly reproducible typing platform for outbreak analysis that can compete with the currently used typing techniques.

Hemoglobin and red blood cells catalyze atom transfer radical polymerization.

Hemoglobin (Hb) is a promiscuous protein that not only transports oxygen, but also catalyzes several biotransformations. A novel in vitro catalytic activity of Hb is described. Bovine Hb and human erythrocytes were found to display ATRPase activity, i.e., they catalyzed the polymerization of vinyl monomers under conditions typical for atom transfer radical polymerization (ATRP). N-isopropylacrylamide (NIPAAm), poly(ethylene glycol) methyl ether acrylate (PEGA), and poly(ethylene glycol) methyl ether methacrylate (PEGMA) were polymerized using organobromine initiators and the reducing agent ascorbic acid in acidic aqueous solution. In order to avoid chain transfer from polymer radicals to Hb's cysteine residues, the accessible cysteines were blocked by a reaction with a maleimide. The formation of polymers with bromine chain ends, relatively low polydispersity indices (PDI), first order kinetics and an increase in the molecular weight of poly(PEGA) and poly(PEGMA) upon conversion indicate that control of the polymerization by Hb occurred via reversible atom transfer between the protein and the growing polymer chain. For poly(PEGA) and poly(PEGMA), the reactions proceeded with a good to moderate degree of control. Sodium dodecyl sulfate (SDS) gel electrophoresis, circular dichroism spectroscopy, and time-resolved ultraviolet-visible (UV-vis) spectroscopy revealed that the protein was stable during polymerization, and only underwent minor conformational changes. As Hb and erythrocytes are readily available, environmentally friendly, and nontoxic, their ATRPase activity is a useful tool for synthetic polymer chemistry. Moreover, this novel activity enhances the understanding of Hb's redox chemistry in the presence of organobromine compounds.

Self-assembled structures from amphiphilic peptides.

Nanotechnology and its applications are strongly influenced by structures self-assembled from a variety of different materials. This review covers nanostructures, including micelles, rod-like micelles, fibers and peptide beads, self-assembled from de novo designed amphiphilic peptides. The latter are promising candidates for the development of nanoscale carrier systems because they are completely composed of amino acids. In addition to designing primary sequences, secondary structure and external parameters are also discussed with respect to their impact on self-assembly. Moreover, the assembly process itself is examined. Potential applications range from gene and drug delivery devices to diagnostics, thereby highlighting the versatility of the system.

Vermamoeba vermiformis resides in water-based heater-cooler units and can enhance Mycobacterium chimaera survival after chlorine exposure.

BACKGROUND: Mycobacterium chimaera colonizes water-based heater-cooler units (HCUs), from which it can spread to patients during surgery. Vermamoeba vermiformis is a free-living waterborne amoeba, which was consistently present within HCUs. AIM: To determine whether these amoebae can be involved in the persistent presence of M. chimaera. METHODS: An in-vitro disinfection model. FINDINGS: Increased survival of M. chimaera was observed after chlorine exposure in the presence of V. vermiformis. Confocal microscopy demonstrated the intracellular presence of M. chimaera in V. vermiformis. CONCLUSION: In this way, V. vermiformis can contribute to the persistent presence of M. chimaera in HCUs. Cleaning and disinfection protocols should take this phenomenon into account.

Use of a smartphone app to inform healthcare workers of hospital policy during a pandemic such as COVID-19: A mixed methods observational study.

OBJECTIVE: To evaluate the use of a COVID-19 app containing relevant information for healthcare workers (HCWs) in hospitals and to determine user experience. METHODS: A smartphone app (Firstline) was adapted to exclusively contain local COVID-19 policy documents and treatment protocols. This COVID-19 app was offered to all HCWs of a 900-bed tertiary care hospital. App use was evaluated with user analytics and user experience in an online questionnaire. RESULTS: A total number of 1168 HCWs subscribed to the COVID-19 app which was used 3903 times with an average of 1 minute and 20 seconds per session during a three-month period. The number of active users peaked in April 2020 with 1017 users. Users included medical specialists (22.3%), residents (16.5%), nurses (22.2%), management (6.2%) and other (26.5%). Information for HCWs such as when to test for SARS-CoV-2 (1214), latest updates (1181), the COVID-19 telephone list (418) and the SARS-CoV-2 / COVID-19 guideline (280) were the most frequently accessed advice. Seventy-one users with a mean age of 46.1 years from 19 different departments completed the questionnaire. Respondents considered the COVID-19 app clear (54/59; 92%), easy-to-use (46/55; 84%), fast (46/52; 88%), useful (52/56; 93%), and had faith in the information (58/70; 83%). The COVID-19 app was used to quickly look up something (43/68; 63%), when no computer was available (15/68; 22%), look up / dial COVID-related phone numbers (15/68; 22%) or when walking from A to B (11/68; 16%). Few respondents felt app use cost time (5/68; 7%). CONCLUSIONS: Our COVID-19 app proved to be a relatively simple yet innovative tool that was used by HCWs from all disciplines involved in taking care of COVID-19 patients. The up-to-date app was used for different topics and had high user satisfaction amongst questionnaire respondents. An app with local hospital policy could be an invaluable tool during a pandemic.

Impact of sink design on bacterial transmission from hospital sink drains to the surrounding sink environment tested using a fluorescent marker.

In hospitals, sinks act as reservoirs for bacterial pathogens. To assess the extent of splashing, fluorescein dye was added to four hospital sinks previously involved in pathogen dispersal to the environment and/or transmission to patients, and one sink that was not. Applying dye to the p-trap or tailpiece did not result in any fluorescent droplets outside of the drain. When applied to the drain, droplets were found in all but one wash basin, and this was more common in the absence of a drain plug. Sink design considerations to install drain plugs, reduce dripping and offset the tap may help to prevent transmission from drains.

MetA is a "thermal fuse" that inhibits growth and protects Escherichia coli at elevated temperatures.

Adaptive stress resistance in microbes is mostly attributed to the expression of stress response genes, including heat-shock proteins. Here, we report a response of E. coli to heat stress caused by degradation of an enzyme in the methionine biosynthesis pathway (MetA). While MetA degradation can inhibit growth, which by itself is detrimental for fitness, we show that it directly benefits survival at temperatures exceeding 50°C, increasing survival chances by more than 1,000-fold. Using both experiments and mathematical modeling, we show quantitatively how protein expression, degradation rates, and environmental stressors cause long-term growth inhibition in otherwise habitable conditions. Because growth inhibition can be abolished with simple mutations, namely point mutations of MetA and protease knockouts, we interpret the breakdown of methionine synthesis as a system that has evolved to halt growth at high temperatures, analogous to "thermal fuses" in engineering that shut off electricity to prevent overheating.

Horseradish peroxidase as a catalyst for atom transfer radical polymerization.

The hemoprotein horseradish peroxidase (HRP) catalyzes the polymerization of N-isopropylacrylamide with an alkyl bromide initiator under conditions of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) in the absence of any peroxide. This is a novel activity of HRP, which we propose to name ATRPase activity. Bromine-terminated polymers with polydispersity indices (PDIs) as low as 1.44 are obtained. The polymerization follows first order kinetics, but the evolution of molecular weight and the PDI upon increasing conversion deviate from the results expected for an ATRP mechanism. Conversion, M(n) and PDI depend on the pH and on the concentration of the reducing agent, sodium ascorbate. HRP is stable during the polymerization and does not unfold or form conjugates.