Comparison of bacteria in different metabolic states by micro-Raman spectroscopy

It was shown that several metabolic states of bacteria with various characteristics such as chemical composition participate in the formation of biofilms. To study the connections and differences among different bacterial metabolic states, five species of bacteria in exponential phase, stationary phase and biofilm have been compared and investigated by micro-Raman spectroscopy. The spectral differences between different metabolic states showed that the chemical composition varied among those metabolic states. Moreover, as can be shown by the spectral differences and principal components (PCs), different species and strains of bacteria behave differently. Furthermore, a principal component analysis (PCA) combined with support vector machines (SVM) was applied to distinguish species of bacteria within the same metabolic states. Our study provides valuable data for the comparison of bacteria between different metabolic states utilizing micro-Raman spectroscopy in combination with chemometrics models

Towards a Harmonized Terminology: A Glossary for Biocide Susceptibility Testing

Disinfection is a key strategy to reduce the burden of infections. The contact of bacteria to biocides—the active substances of disinfectants—has been linked to bacterial adaptation and the development of antimicrobial resistance. Currently, there is no scientific consensus on whether the excessive use of biocides contributes to the emergence and spread of multidrug resistant bacteria. The comprehensive analysis of available data remains a challenge because neither uniform test procedures nor standardized interpretive criteria nor harmonized terms are available to describe altered bacterial susceptibility to biocides. In our review, we investigated the variety of criteria and the diversity of terms applied to interpret findings in original studies performing biocide susceptibility testing (BST) of field isolates. An additional analysis of reviews summarizing the knowledge of individual studies on altered biocide susceptibility provided insights into currently available broader concepts for data interpretation. Both approaches pointed out the urgent need for standardization. We, therefore, propose that the well-established and approved concepts for interpretation of antimicrobial susceptibility testing data should serve as a role model to evaluate biocide resistance mechanisms on a single cell level. Furthermore, we emphasize the adaptations necessary to acknowledge the specific needs for the evaluation of BST data. Our approach might help to increase scientific awareness and acceptance

Label-free multimodal imaging of infected Galleria mellonella larvae

Non-linear imaging modalities have enabled us to obtain unique morpho-chemical insights into the tissue architecture of various biological model organisms in a label-free manner. However, these imaging techniques have so far not been applied to analyze the Galleria mellonella infection model. This study utilizes for the first time the strength of multimodal imaging techniques to explore infection-related changes in the Galleria mellonella larvae due to massive E. faecalis bacterial infection. Multimodal imaging techniques such as fluorescent lifetime imaging (FLIM), coherent anti-Stokes Raman scattering (CARS), two-photon excited fluorescence (TPEF), and second harmonic generation (SHG) were implemented in conjunction with histological HE images to analyze infection-associated tissue damage. The changes in the larvae in response to the infection, such as melanization, vacuolization, nodule formation, and hemocyte infiltration as a defense mechanism of insects against microbial pathogens, were visualized after Enterococcus faecalis was administered. Furthermore, multimodal imaging served for the analysis of implant-associated biofilm infections by visualizing biofilm adherence on medical stainless steel and ePTFE implants within the larvae. Our results suggest that infection-related changes as well as the integrity of the tissue of G. mellonella larvae can be studied with high morphological and chemical contrast in a label-free manner

The Care Work of Access

Current approaches to AI and Assistive Technology (AT) often foreground task completion over other encounters such as expressions of care. Our paper challenges and complements such task-completion approaches by attending to the care work of access—the continual affective and emotional adjustments that people make by noticing and attending to one another. We explore how this work impacts encounters among people with and without vision impairments who complete tasks together. We find that bound up in attempts to get things done are concerns for one another and how well people are doing together. Reading this work through emerging disability studies and feminist STS scholarship, we account for two important forms of work that give rise to access: (1) mundane attunements and (2) noninnocent authorizations. Together these processes work as sensitizing concepts to help HCI scholars account for the ways that intelligent ATs both produce access while sometimes subverting people with disabilities

Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel

Dark matter lighter than 10  GeV/c2 encompasses a promising range of candidates. A conceptual design for a new detector, DarkSide-LowMass, is presented, based on the DarkSide-50 detector and progress toward DarkSide-20k, optimized for a low-threshold electron-counting measurement. Sensitivity to light dark matter is explored for various potential energy thresholds and background rates. These studies show that DarkSide-LowMass can achieve sensitivity to light dark matter down to the solar neutrino fog for GeV-scale masses and significant sensitivity down to 10  MeV/c2 considering the Migdal effect or interactions with electrons. Requirements for optimizing the detector’s sensitivity are explored, as are potential sensitivity gains from modeling and mitigating spurious electron backgrounds that may dominate the signal at the lowest energies

Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel

Dark matter lighter than 10 GeV/c$^2$ encompasses a promising range of candidates. A conceptual design for a new detector, DarkSide-LowMass, is presented, based on the DarkSide-50 detector and progress toward DarkSide-20k, optimized for a low-threshold electron-counting measurement. Sensitivity to light dark matter is explored for various potential energy thresholds and background rates. These studies show that DarkSide-LowMass can achieve sensitivity to light dark matter down to the solar neutrino floor for GeV-scale masses and significant sensitivity down to 10 MeV/c$^2$ considering the Migdal effect or interactions with electrons. Requirements for optimizing the detector's sensitivity are explored, as are potential sensitivity gains from modeling and mitigating spurious electron backgrounds that may dominate the signal at the lowest energies

Evaluation of treatment options for Enterococcus faecalis endocarditis by assessing synergistic and anti-biofilm effects

Enterococcus faecalis is increasingly found as the causative organism of infective endocarditis, an infection of the heart valves with mortality rates up to 30 %. Traditionally, antibiotic combination therapy has been used for treatment of E. faecalis endocarditis, but it is still not clear if and which combination therapy is truly superior to monotherapy. Further, the treatment-resistant nature of infective endocarditis strongly suggests the involvement of biofilms. The main aim of this thesis was therefore to compare the recommended but nephrotoxic standard gentamicin/ampicillin combination with the recently recommended alternative ceftriaxone/ampicillin and the novel possibly effective ceftaroline/ampicillin combination by evaluating their synergistic interactions against planktonic and biofilm-embedded enterococci. On biofilm level, no synergistic effects between neither a cephalosporin- nor aminoglycoside-based combination could be observed, since none of the antibiotic combinations succeeded in eradicating mature E. faecalis biofilms. However, in planktonic E. faecalis cells synergism could be detected for ceftriaxone/ampicillin both in vitro and in a larval model, while for ceftaroline/ampicillin synergism was only detected in vitro. Gentamicin/ampicillin showed no synergistic effects for both in vitro and in vivo synergy analysis. In conclusion, the choice of antibiotic combination or monotherapy for treatment of E. faecalis endocarditis should ideally be based on the maturity and progression of biofilm development. While patients with an acute bacteraemia may benefit from a synergistic antibiotic combination therapy, combination therapy does not seem to be superior to monotherapy for treatment of mature biofilms. The results of this thesis favour the replacement of gentamicin/ampicillin by a cephalosporin-based combination due to the lack of synergistic effects. However, novel cephalosporins, i.e. ceftaroline, do not seem to provide additional benefit

In Vitro Synergism of Penicillin and Ceftriaxone against Enterococcus faecalis

Enterococcus faecalis infective endocarditis is commonly treated with intravenous ampicillin/ceftriaxone combination therapy. Ampicillin, however, is unsuitable for outpatient parenteral antibiotic therapy (OPAT) regimens due to its instability in 24 h continuous infusors, and has been successfully replaced by benzylpenicillin used together with ceftriaxone in a few small case series. Since in vitro synergy data of penicillin/ceftriaxone against E. faecalis are still lacking, checkerboard assays were performed for 28 clinical E. faecalis isolates and one laboratory standard strain. Synergistic effects (both lowest and median FICI) were observed for penicillin/ceftriaxone in 15/29 isolates, while ampicillin/ceftriaxone exhibited synergism in 22/29 isolates. For isolates with ceftriaxone MICs ≤ 256 mg/L, the addition of free ceftriaxone trough concentrations to penicillin or ampicillin resulted in comparable synergistic effects for both combinations. In contrast, for isolates with ceftriaxone MICs ≥ 512 mg/L free ceftriaxone trough concentrations were only sufficient to exhibit synergistic effects in combination with ampicillin, but not penicillin. This study suggests that benzylpenicillin/ceftriaxone would be expected to be suitable for the OPAT treatment of enterococcal endocarditis for E. faecalis isolates with ceftriaxone MICs ≤ 256 mg/L. However, combination therapy would be expected to provide no advantage over benzylpenicillin monotherapy for isolates with ceftriaxone MICs ≥ 512 mg/L. Further investigation is required to analyse the relationship between ceftriaxone susceptibility and penicillin/ceftriaxone synergy, especially for isolates with ceftriaxone MICs of 64 to 512 mg/L