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Abstract Background Specialist palliative care teams (SPCTs) have significant benefits for patients with advanced disease or frailty, including improved quality of life, greater satisfaction with care, and less potentially inappropriate care at the end of life. Experienced SPCTs are recognised to have higher referral rates compared to novice teams. The aim of this study was to assess the development of hospital-wide integration of specialist palliative care (PC) and of SPCTs in Dutch hospitals between 2014 and 2020. Methods Three cross-sectional surveys of SPCTs in Dutch hospitals were conducted in 2015, 2018 and 2021. Key members of the hospital SPCTs completed questionnaires about the preceding year that included items on hospital and PC program characteristics, hospital-wide integration of specialist PC, and SPCT characteristics (92 hospitals in 2015, 79 in 2018 and 74 in 2021). The analysis included hospitals with an operational SPCT, as determined by providing inpatient PC consultation services. Univariate analyses compared hospitals and SPCTs by year. Significance was determined by p-values

Antimicrobial resistance (AMR) poses a significant global threat to public health systems, rendering antibiotics ineffective in treating infectious diseases. Combined use of bio compounds, including bacteriophages and plant extracts, is an attractive approach to controlling antibiotic resistance. In this study, the combination of phage cocktail (Isf-Pm1 and Isf-Pm2) and Alhagi maurorum crude extract (AME) was investigated in controlling biofilm-forming multi-drug resistant P. mirabilis isolates, in vitro and a phantom bladder model. The combination of AME and phage cocktails demonstrated no significant disparity in its ability to inhibit quorum sensing (QS) when compared to the individual control of AME alone. Following treatment with the combination of phage cocktail and AME at a 125 μg/mL concentration, the MDR P. mirabilis biofilm biomass was notably reduced by 73% compared to the control (P< 0.0001). The anti-biofilm effect was confirmed by Scanning Electron Microscopy (SEM). Moreover, in a bladder phantom model, there was a considerable decrease in encrustation levels compared to the control. The combined treatment resulted in a 1.85 logarithmic reduction in bacterial adhesion to Vero cells compared to the control. The real-time PCR results indicated significant downregulation of QS- and adhesion-related gens. The phage therapy, combined with AME, holds promising potential in reducing biofilm formation.

ABSTRACT Bacterial black spot, caused by Acidovorax valerianellae, is responsible for significant yield losses in lamb’s lettuce (Valerianella locusta) in many producing countries, especially Europe. Currently, no resistant varieties of V. locusta are available that effectively control the disease under field conditions. Bacteriophage-based biocontrol has been suggested as a sustainable and natural alternative strategy to combat bacterial pathogens. In this study, novel phages infecting A. valerianellae and Acidovorax cattleyae, Alfacinha1, Alfacinha3, Acica, and Aval, were isolated and characterized. Based on comparative genomics, these phages represent three new phage genera. Aval and Acica phages revealed genomic features characteristic of temperate lifestyle, encoding toxins likely associated with lysogenic conversion, which contrasts with Alfacinha1 and Alfacinha3. The latter was selected for application as a biocontrol agent during seed steeping. This phage reaches an 87% reduction in the A. valerianellae concentration on artificially infested seeds. Importantly, this reduction results in an increased germination rate from 58.9% to 93.3%. Moreover, the infected seedlings had a dramatic reduction in vigor index after 22 days of growth, whereas the phage-treated ones had a vigor index similar to the negative control, reinforcing the ability of bacteriophages to effectively reduce disease progression. We further evaluated the impact of lipopolysaccharides in phage suspensions on the development of seedlings. Here, we demonstrated that the presence of lipopolysaccharides do have an impact on seedling development, significantly reducing the number of roots developed. This study shows how genomic analyses and tailored bioassays represent an essential route to ensure safe phage application and demonstrates the potential of a phage-based biocontrol strategy against A. valerianellae.IMPORTANCEBacteria continue to globally cause serious damage to a variety of crops. One example is a bacterial black spot of lamb’s lettuce caused by Acidovorax valerianellae. It has spread across Europe, resulting in economic losses of at least 10% in tonnage annually. Faced with the inefficiency of conventional control methods, an alternative and sustainable strategy based on the use of bacteriophages was pursued in this study. We present for the first time the isolation and characterization of A. valerianellae-specific phages. Moreover, we assessed their biocontrol potential in seed decontamination since the disease primarily spreads from seeds to seedlings. Interestingly, seed treatment with one of our phages reaches an 87% reduction in bacterial concentration. More importantly, this reduction results in an increased germination rate from 58.9% to 93.3%. Finally, our study demonstrated for the first time the need for removing endotoxins from phage suspensions as they impact plant development when used as a biocontrol agent.

Given the increasing threat of antimicrobial resistance, scientists are urgently seeking adjunct antimicrobial strategies, such as phage therapy (PT). However, despite promising results for the treatment of musculoskeletal infections in our center, crucial knowledge gaps remain. Therefore, a prospective observational study (PHAGEFORCE) and a multidisciplinary approach was set up to achieve and optimize standardized treatment guidelines. At our center, PT is strictly controlled and monitored by a multidisciplinary taskforce. Each phage treatment follows the same pathway to ensure standardization and data quality. Within the PHAGEFORCE framework, we established a testing platform to gain insight in the safety and efficacy of PT, biodistribution, phage kinetics and the molecular interaction between phages and bacteria. The draining fluid is collected to determine the phage titer and bacterial load. In addition, all bacterial isolates are fully characterized by genome sequencing to monitor the emergence of phage resistance. We hereby present a standardized bench-to-bedside protocol to gain more insight in the kinetics and dynamics of PT for musculoskeletal infections.

Pictorial awareness is addressed through experimental phenomenology involving over 90 naïve participants. Since one can’t look at the “same” picture twice the study uses one-shot trials. The participant’s fascination for the duration of a session is held through the artistic principle of theme and variation. Six variations focus on the theme of pictorial geometry, both two-dimensional and three-dimensional. Major findings are: Idiosyncratic deviations from veridical are huge as compared to common textbook “effects.” Observers wield arbitrary heuristics for tasks that are “formally related.” The assumption of a common formal framework is apparently unsound. The notion of “inverse optics” is misleading. A fair fraction of the population appears to lack monocular stereopsis as intuitive awareness. It suggests an as-yet unrecognized, but perhaps common variety of aphantasia.

Staphylococcus aureus´ biofilm-forming ability and rapid resistance development pose a significant challenge to successful treatment, particularly in postoperative complications, emphasizing the need for enhanced therapeutic strategies. Bacteriophage (phage) therapy has reemerged as a promising and safe option to combat multidrug-resistant bacteria. However, questions regarding the efficacy of phages against biofilms and the development of phage resistance require further evaluation. Expanding on the adaptable and evolutionary characteristics of phages, we introduce an evolutionary approach to enhance the activity of S. aureus phages against biofilms. Unlike other in vitro directed evolution methods performed in planktonic cultures, we employed pre-stablished biofilms to do a serial-passage assay to evolve phages monitored by real-time isothermal microcalorimetry (IMC). The evolved phages demonstrated an expanded host range, with the CUB_MRSA-COL_R9 phage infecting 83% of strains in the collection (n = 72), surpassing the ISP phage, which represented the widest host range (44%) among the ancestral phages. In terms of antimicrobial efficacy, IMC data revealed superior suppression of bacterial growth by the evolved phages compared to the ancestral CUB-M and/or ISP phages against the respective bacterial strain. The phage cocktail exhibited higher efficacy, achieving over 90% suppression relative to the growth control even after 72 h of monitoring. Biofilm cell-counts, determined by RT-qPCR, confirmed the enhanced antibiofilm performance of evolved phages with no biofilm regrowth up to 48 h in treated MRSA15 and MRSA-COL strains. Overall, our results underscore the potential of biofilm-adapted phage cocktails to improve clinical outcomes in biofilm-associated infections, minimizing the emergence of resistance and lowering the risk of infection relapse. However, further investigation is necessary to evaluate the translatability of our results from in vitro to in vivo models, especially in the context of combination therapy with the current standard of care treatment.

This study investigates the potential of using bacteriophages to control foodborne pathogen biofilms on stainless steel surfaces in the food industry. Biofilm-forming bacteria can attach to stainless steel surfaces, rendering them difficult to eradicate even after a thorough cleaning and sanitizing procedures. Bacteriophages have been proposed as a possible solution, as they can penetrate biofilms and destroy bacterial cells within, reducing the number of viable bacteria and preventing the growth and spread of biofilms. This systematic review and meta-analysis evaluates the potential of bacteriophages against different biofilm-forming foodborne bacteria, including Cronobacter sakazakii, Escherichia coli, Staphylococcus aureus, Pseudomonas fluorescens, Pseudomonas aeruginosa and Listeria monocytogenes. Bacteriophage treatment generally causes a significant average reduction of 38 % in biofilm formation of foodborne pathogens on stainless steel. Subgroup analyses revealed that phages are more efficient in long-duration treatment. Also, applying a cocktail of phages is 1.26-fold more effective than applying individual phages. Phages at concentrations exceeding 107 PFU/ml are significantly more efficacious in eradicating bacteria within a biofilm. The antibacterial phage activity decreases substantially by 3.54-fold when applied at 4 °C compared to temperatures above 25 °C. This analysis suggests that bacteriophages can be a promising solution for controlling biofilms in the food industry.