A Bioluminescence-Based Ex Vivo Burn Wound Model for Real-Time Assessment of Novel Phage-Inspired Enzybiotics.

The silent pandemic of antibiotic resistance is thriving, prompting the urgent need for the development of new antibacterial drugs. However, within the preclinical pipeline, in vitro screening conditions can differ significantly from the final in vivo settings. To bridge the gap between in vitro and in vivo assays, we developed a pig-skin-based bioluminescent ex vivo burn wound infection model, enabling real-time assessment of antibacterials in a longitudinal, non-destructive manner. We provide a proof-of-concept for A. baumannii NCTC13423, a multidrug-resistant clinical isolate, which was equipped with the luxCDABE operon as a reporter using a Tn7-based tagging system. This bioluminescence model provided a linear correlation between the number of bacteria and a broad dynamic range (104 to 109 CFU). This longitudinal model was subsequently validated using a fast-acting enzybiotic, 1D10. Since this model combines a realistic, clinically relevant yet strictly controlled environment with real-time measurement of bacterial burden, we put forward this ex vivo model as a valuable tool to assess the preclinical potential of novel phage-inspired enzybiotics.

Communication management in social responsibility programs in the mining sector / Gestión de la comunicación en programas de responsabilidad social en el sector minero

RESUMEN La responsabilidad social, como una de las respuestas a los actuales conflictos socioambientales, implica esfuerzos adicionales de las organizaciones para fortalecer su capacidad de gestión. Esto sucede, de manera especial, en las compañías mineras, cuyas actividades comprometen el uso de recursos de comunidades, entre ellos los naturales. Esta investigación analizó los aportes que la gestión de comunicaciones hace al relacionamiento con las comunidades en el marco de dos programas de responsabilidad social de los proyectos mineros Quebradona y Gramalote (ubicados en Antioquia, Colombia), adscritos a la compañía Anglogold Ashanti y ganadores del Premio Sello Social a la Minería en Antioquia, siendo dos de los proyectos con mayor exigencia y veeduría ciudadana en la región. Desde una mirada con predominancia interpretativa, y acudiendo a la revisión de documentos y entrevistas a jefes de áreas sociales, comunicadores, beneficiarios y líderes ambientales, se concluyó que el análisis del entorno, la visibilización de los programas y la mediación en los conflictos socioambientales son los principales aportes de los comunicadores en los proyectos mineros.

ABSTRACT Social responsibility, as one of the responses to current sock-environmental conflicts, implies additional efforts by organizations to strengthen their management capacity. This happens, especially, in mining companies, our activities compromise the use of community resources, including natural resources. This research analyzed the contributions that communications management makes to relations with communities within the framework of two social responsibility programs of the Quebradona and Gramalote mining projects (located in Antioquia, Colombia), attached to the company Anglogold Ashanti and winners of the Premio Sello Social a la Minería en Antioquia, being two of the projects with the highest demand and citizen oversight in the region. From an interpretive perspective and going to the review of documents and interviews with heads of social areas, communicators, beneficiaries, and environmental leaders, it was concluded that the analysis of the environment, the visibility of the programs and mediation in socio-environmental conflicts are the main contributions of communicators in mining projects.

A Comparison of Caregiver Burden of Patients with Advanced Cancer in Different Palliative Cancer Care Settings.

Background: Informal caregivers may experience a significant burden while caring for cancer patients. Little is known about how caregiver burden varies across different palliative cancer care settings and the factors influencing it. Objectives: We compared the severity of caregiver subjective stress burden (emotional impact) among caregivers of patients seen in the outpatient supportive care center (SCC) with those being cared for in the acute palliative care unit (PCU). Secondary aims were to compare other caregiver burden dimensions, quality of life, and any association of caregiver subjective stress burden to various patient and caregiver factors. Setting and Design: Eligible patients and their informal caregivers in the SCC or PCU at a comprehensive cancer center in the USA were approached and enrolled. The Montgomery-Borgatta Caregiver Burden Scale and the Short-form 36 were used to measure burden and quality of life. Multivariate general linear regression was employed to evaluate the effect of covariates on subjective stress burden. Results: Ninety-eight dyads in the SCC and 74 dyads in the PCU were enrolled. PCU caregivers reported worse subjective stress burden (p = 0.0029) and mental health (p = 0.0299). Multivariate analysis showed correlations between subjective stress burden and caregivers' objective burden (p = 0.0136), subjective demand burden (p ≤ 0.0001), mental health (p = 0.0074), duration of caregiving (p = 0.0680), education (p = 0.0192) and with patients' anxiety (p = 0.0003) and current/recent cancer treatment (p = 0.0579). Conclusion: PCU caregivers demonstrated worse emotional burden and mental health than those in the SCC. More research is needed to tailor interventions for various caregiver burden dimensions. NCI Clinical Trial Registration Number ID: NCI-2019-01197.

Characterization of Clinical MRSA Isolates from Northern Spain and Assessment of Their Susceptibility to Phage-Derived Antimicrobials.

Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent nosocomial pathogen, causing a wide range of diseases. The increased frequency of MRSA isolates in hospitals and the emergence of vancomycin resistance have sparked the search for new control strategies. This study aimed to characterize sixty-seven MRSA isolates collected from both infected patients and asymptomatic carriers in a Spanish hospital. RAPD-PCR allowed the identification of six genetic patterns. We also investigated the presence of genes involved in producing adhesins, toxins and the capsule; the biofilm; and antimicrobial resistance. A notable percentage of the isolates carried virulence genes and showed medium-high ability to form biofilms. Next, we assessed the strains' susceptibility to two phages (phiIPLA-C1C and phiIPLA-RODI) and one endolysin (LysRODI). All strains were resistant to phiIPLA-C1C, and most (70.2%) were susceptible to phiIPLA-RODI. Regarding LysRODI, all strains displayed susceptibility, although to varying degrees. There was a correlation between endolysin susceptibility and the random amplification of polymorphic DNA (RAPD) profile or the presence of some virulence genes (fnbA, eta, etb, PVL and czr), but that was not observed with biofilm-forming ability, strain origin or phage sensitivity. Taken together, these findings can help to explain the factors influencing endolysin effectiveness, which will contribute to the development of efficient therapies targeting MRSA infections.

Preliminary Assessment of Visible, Near-Infrared, and Short-Wavelength-Infrared Spectroscopy with a Portable Instrument for the Detection of Staphylococcus aureus Biofilms on Surfaces.

Bacterial biofilms constitute a major source of sanitary problems and economic losses in the food industry. Indeed, biofilm removal may require intense mechanical cleaning procedures or very high concentrations of disinfectants or both, which can be damaging to the environment and human health. This study assessed the efficacy of a technique based on spectroscopy in the visible, near-infrared, and short-wavelength infrared range for the quick detection of biofilms formed on polystyrene by the pathogenic bacterium Staphylococcus aureus. To do that, biofilms corresponding to three S. aureus strains, which differed in biofilm-forming ability and composition of the extracellular matrix, were allowed to develop for 5 or 24 h, representing an active formation stage and mature biofilms, respectively. Spectral analysis of the samples, corresponding to three biological replicates of each condition, was then performed by using a portable device. The results of these experiments showed that partial least-squares discriminant analysis of the spectral profile could discriminate between surfaces containing attached bacterial biomass and noninoculated ones. In this model, the two first principal components accounted for 39 and 19% of the variance and the estimated error rate stabilized after four components. Cross-validation accuracy of this assessment was 100%. This work lays the foundation for subsequent development of a spectroscopy-based protocol that allows biofilm detection on food industrial surfaces.

Comparative analysis of different preservation techniques for the storage of Staphylococcus phages aimed for the industrial development of phage-based antimicrobial products.

Bacteriophages have been proven as effective antimicrobial agents in the treatment of infectious diseases and in other biocontrol applications including food preservation and disinfection. The extensive use of bacteriophages requires improved methodologies for medium- and long-term storage as well as for easy shipping. To this aim, we have determined the stability of four Staphylococcus phages (phiIPLA88, phiIPLA35, phiIPLA-RODI and phiIPLA-C1C) with antimicrobial potential at different temperatures (20°C/25°C, 4°C, -20°C, -80°C, -196°C) and during lyophilization (freeze drying) using several stabilizing additives (disaccharides, glycerol, sorbitol and skim milk). Differences between phages were observed at different temperatures (20°C/25°C, 4°C and -20°C), where phages were less stable. At lower temperatures (-80°C and -196°C), all phages showed good viability after 24 months regardless of the stabilizer. Differences between phages were also observed after lyophilization although the addition of skim milk yielded a dry powder with a stable titer after 24 months. As an alternative to facilitate storage and transportation, phage encapsulation has been also explored. Phage phiIPLA-RODI encapsulated in alginate capsules retained high viability when stored at 4°C for 6 months and at 20°C for 1 month. Moreover, the spray-dryer technique allowed obtaining dry powders containing viable encapsulated phages (phiIPLA-RODI and phiIPLA88) in both skim milk and trehalose for 12 months at 4°C. Storage of phages at 20°C was less effective; in fact, phiIPLA88 was stable for at least 12 months in trehalose but not in skim milk, while phiIPLA-RODI was stable only for 6 months in either stabilizer. These results suggest that encapsulated phages might be a suitable way for shipping phages.

Real-Time Assessment of Staphylococcus aureus Biofilm Disruption by Phage-Derived Proteins.

A current focus of research is the development of new tools for removing bacterial biofilms in industrial settings. Bacteriophage-encoded proteins, such as endolysins, virion-associated peptidoglycan hydrolases, and exopolysaccharide depolymerases, have been shown to be efficient against these structures. However, the current screening techniques for the identification of antibiofilm properties of phage-derived proteins have important shortcomings. The aim of this work was to use the rapid, reproducible and accurate technology "real-time cell analyzer" for screening and comparing the antibiofilm ability of four phage-derived compounds, three lytic proteins (LysH5, CHAP-SH3b, and HydH5-SH3b) and one exopolysaccharide depolymerase (Dpo7) against Staphylococcus aureus biofilms, which have been associated with recurrent contamination of food products. The data generated after biofilm treatment allowed for the calculation of different antibiofilm parameters: (1) the minimum biofilm eradicating concentration that removes 50% of the biofilm (ranging from 3.5 ± 1.1 to 6.6 ± 0.5 µM), (2) the lowest concentration needed to observe an antibiofilm effect (∼1.5 µM for all the proteins), and (3) the specific antibiofilm activity and the percentage of biofilm removal that revealed LysH5 as the best antibiofilm compound. Overall, this technology might be used to quickly assess and compare by standardized parameters the disaggregating activity of phage antibiofilm proteins.

'Life does not make it easy to breast-feed': using the socio-ecological framework to determine social breast-feeding obstacles in a low-income population in Tijuana, Mexico.

OBJECTIVE: Breast-feeding rates reflect sociodemographic discrepancies. In Mexico, exclusive breast-feeding under 6 months of age has deteriorated among the poor, rural and indigenous populations from 1999 to 2012. Our objective of the present study was to identify the main social obstacles to breast-feeding in a low-income population in Tijuana, Mexico. DESIGN: Qualitative study using a socio-ecological framework for data collection. SETTING: Low-income communities in Tijuana, Mexico. SUBJECTS: Mothers (n 66), fathers (n 11), grandparents (n 27) and key informants (n 25). RESULTS: One hundred and twenty-nine individuals participated in the study: six focus groups (n 53) and fifty-one interviews among mothers, fathers and grandparents; and twenty-five interviews among key informants. Seven social themes were identified: (i) embarrassment to breast-feed in public; (ii) migrant experience; (iii) women's role in society; (iv) association of formula with higher social status; (v) marketing by the infant food industry; (vi) perception of a non-breast-feeding culture; and (vii) lack of breast-feeding social programmes. CONCLUSIONS: Socio-structural factors influence infant feeding practices in low-income communities in Tijuana. We hypothesize that messages emphasizing Mexican traditions along with modern healthy practices could help to re-establish and normalize a breast-feeding culture in this population. The target audience for these messages should not be limited to mothers but also include family, health-care providers, the work environment and society as a whole.

Comparison of the disparity between Talairach and MNI coordinates in functional neuroimaging data: validation of the Lancaster transform.

Spatial normalization of neuroimaging data is a standard step when assessing group effects. As a result of divergent analysis procedures due to different normalization algorithms or templates, not all published coordinates refer to the same neuroanatomical region. Specifically, the literature is populated with results in the form of MNI or Talairach coordinates, and their disparity can impede the comparison of results across different studies. This becomes particularly problematic in coordinate-based meta-analyses, wherein coordinate disparity should be corrected to reduce error and facilitate literature reviews. In this study, a quantitative comparison was performed on two corrections, the Brett transform (i.e., "mni2tal"), and the Lancaster transform (i.e., "icbm2tal"). Functional magnetic resonance imaging (fMRI) data acquired during a standard paired associates task indicated that the disparity between MNI and Talairach coordinates was better reduced via the Lancaster transform, as compared to the Brett transform. In addition, an activation likelihood estimation (ALE) meta-analysis of the paired associates literature revealed that a higher degree of concordance was obtained when using the Lancaster transform in the form of fewer, smaller, and more intense clusters. Based on these results, we recommend that the Lancaster transform be adopted as the community standard for reducing disparity between results reported as MNI or Talairach coordinates, and suggest that future spatial normalization strategies be designed to minimize this variability in the literature.