Infection-specific PET imaging with 18F-fluorodeoxysorbitol and 2-[18F]F-ρ-aminobenzoic acid: An extended diagnostic tool for bacterial and fungal diseases

IntroductionSuspected infectious diseases located in difficult-to-access sites can be challenging due to the need for invasive procedures to isolate the etiological agent. Positron emission tomography (PET) is a non-invasive imaging technology that can help locate the infection site. The most widely used radiotracer for PET imaging (2-deoxy-2[18F] fluoro-D-glucose: [18F]FDG) shows uptake in both infected and sterile inflammation. Therefore, there is a need to develop new radiotracers able to specifically detect microorganisms.MethodsWe tested two specific radiotracers: 2-deoxy-2-[18F]-fluoro-D-sorbitol ([18F]FDS) and 2-[18F]F-ρ-aminobenzoic acid ([18F]FPABA), and also developed a simplified alternative of the latter for automated synthesis. Clinical and reference isolates of bacterial and yeast species (19 different strains in all) were tested in vitro and in an experimental mouse model of myositis infection.Results and discussionNon-lactose fermenters (Pseudomonas aeruginosa and Stenotrophomonas maltophilia) were unable to take up [18F]FDG in vitro. [18F]FDS PET was able to visualize Enterobacterales myositis infection (i.e., Escherichia coli) and to differentiate between yeasts with differential assimilation of sorbitol (i.e., Candida albicans vs. Candida glabrata). All bacteria and yeasts tested were detected in vitro by [18F]FPABA. Furthermore, [18F]FPABA was able to distinguish between inflammation and infection in the myositis mouse model (E. coli and Staphylococcus aureus) and could be used as a probe for a wide variety of bacterial and fungal species

Enseñanza remota de emergencia ante la pandemia Covid-19 en Educación Media Superior y Educación Superior

Este trabajo tiene por objetivo realizar una aproximación a las experiencias del profesorado y estudiantado de Educación Media y Superior en torno a la estrategia de enseñanza implementada durante la emergencia sanitaria por Covid-19. La muestra se integró por 44 docentes y 116 estudiantes originarios de un municipio del sur del estado de Sonora, México. Desde el punto de vista teórico se atiende a los principios de la Enseñanza Remota de Emergencia para enfrentar la crisis a través del trabajo escolar mediado por tecnología. Se diseñó un cuestionario ad hoc para explorar: a) el uso de dispositivos, conectividad y espacios alternativos de instrucción para dar continuidad a los estudios, b) la implementación de los recursos tecnológicos con base en la experiencia, dificultades y preparación, c) evaluación y apoyo recibido y d) adaptación y proyección de los aprendizajes. Los resultados evidencian el uso de laptop y teléfono inteligente como los dispositivos de mayor uso para el estudio, y el envío y recepción de información respectivamente. Además, se señala el incremento de tiempo dedicación y dificultades para la recepción-evaluación de las actividades escolares tanto en docentes como estudiantes. En cuanto al apoyo institucional la habilitación de cursos, softwares y plataformas virtuales representan las principales acciones para dar continuidad a los estudios. Destacando el esfuerzo, voluntad, manejo de tecnología, cambios de dinámica respecto al rol y la revalorización de las clases presenciales como los principales aprendizajes durante el confinamiento

Enseñanza remota de emergencia ante la pandemia Covid-19 en Educación Media Superior y Educación Superior

Este trabajo tiene por objetivo realizar una aproximación a las experiencias del profesorado y estudiantado de Educación Media y Superior en torno a la estrategia de enseñanza implementada durante la emergencia sanitaria por Covid-19. La muestra se integró por 44 docentes y 116 estudiantes originarios de un municipio del sur del estado de Sonora, México. Desde el punto de vista teórico se atiende a los principios de la Enseñanza Remota de Emergencia para enfrentar la crisis a través del trabajo escolar mediado por tecnología. Se diseñó un cuestionario ad hoc para explorar: a) el uso de dispositivos, conectividad y espacios alternativos de instrucción para dar continuidad a los estudios, b) la implementación de los recursos tecnológicos con base en la experiencia, dificultades y preparación, c) evaluación y apoyo recibido y d) adaptación y proyección de los aprendizajes. Los resultados evidencian el uso de laptop y teléfono inteligente como los dispositivos de mayor uso para el estudio, y el envío y recepción de información respectivamente. Además, se señala el incremento de tiempo dedicación y dificultades para la recepción-evaluación de las actividades escolares tanto en docentes como estudiantes. En cuanto al apoyo institucional la habilitación de cursos, softwares y plataformas virtuales representan las principales acciones para dar continuidad a los estudios. Destacando el esfuerzo, voluntad, manejo de tecnología, cambios de dinámica respecto al rol y la revalorización de las clases presenciales como los principales aprendizajes durante el confinamiento

In vivo monitoring of Staphylococcus aureus biofilm infections and antimicrobial therapy by [18F]fluoro-deoxyglucose–MicroPET in a mouse model

A mouse model was developed for in vivo monitoring of infection and the effect of antimicrobial treatment against Staphylococcus aureus biofilms, using the [18F]fluoro-deoxyglucose–MicroPET ([18F]FDG-MicroPET) image technique. In the model, sealed Vialon catheters were briefly precolonized with S. aureus strains ATCC 15981 or V329, which differ in cytotoxic properties and biofilm matrix composition. After subcutaneous implantation of catheters in mice, the S. aureus strain differences found in bacterial counts and the inflammatory reaction triggered were detected by the regular bacteriological and histological procedures and also by [18F]FDG-MicroPET image signal intensity determinations in the infection area and regional lymph node. Moreover, [18F]FDG-MicroPET imaging allowed the monitoring of the rifampin treatment effect, identifying the periods of controlled infection and those of reactivated infection due to the appearance of bacteria naturally resistant to rifampin. Overall, the mouse model developed may be useful for noninvasive in vivo determinations in studies on S. aureus biofilm infections and assessment of new therapeutic approaches.This work was supported by grants from Gobierno de Navarra “IIM13002.RI1” and MICINN “CIT-010000-2009-32”

Soil properties explain tree growth and mortality, but not biomass, across phosphorus-depleted tropical forests

We observed strong positive relationships between soil properties and forest dynamics of growth and mortality across twelve primary lowland tropical forests in a phosphorus-poor region of the Guiana Shield. Average tree growth (diameter at breast height) increased from 0.81 to 2.1 mm yr-1 along a soil texture gradient from 0 to 67% clay, and increasing metal-oxide content. Soil organic carbon stocks in the top 30 cm ranged from 30 to 118 tons C ha-1, phosphorus content ranged from 7 to 600 mg kg-1 soil, and the relative abundance of arbuscular mycorrhizal fungi ranged from 0 to 50%, all positively correlating with soil clay, and iron and aluminum oxide and hydroxide content. In contrast, already low extractable phosphorus (Bray P) content decreased from 4.4 to <0.02 mg kg-1 in soil with increasing clay content. A greater prevalence of arbuscular mycorrhizal fungi in more clayey forests that had higher tree growth and mortality, but not biomass, indicates that despite the greater investment in nutrient uptake required, soils with higher clay content may actually serve to sustain high tree growth in tropical forests by avoiding phosphorus losses from the ecosystem. Our study demonstrates how variation in soil properties that retain carbon and nutrients can help to explain variation in tropical forest growth and mortality, but not biomass, by requiring niche specialization and contributing to biogeochemical diversification across this region

Nutritional interventions with bacillus coagulans improved glucose metabolism and hyperinsulinemia in mice with acute intermittent porphyria

Acute intermittent porphyria (AIP) is a metabolic disorder caused by mutations in the porphobilinogen deaminase (PBGD) gene, encoding the third enzyme of the heme synthesis pathway. Although AIP is characterized by low clinical penetrance (~1% of PBGD mutation carriers), patients with clinically stable disease report chronic symptoms and frequently show insulin resistance. This study aimed to evaluate the beneficial impact of nutritional interventions on correct carbohydrate dysfunctions in a mouse model of AIP that reproduces insulin resistance and altered glucose metabolism. The addition of spores of Bacillus coagulans in drinking water for 12 weeks modified the gut microbiome composition in AIP mice, ameliorated glucose tolerance and hyperinsulinemia, and stimulated fat disposal in adipose tissue. Lipid breakdown may be mediated by muscles burning energy and heat dissipation by brown adipose tissue, resulting in a loss of fatty tissue and improved lean/fat tissue ratio. Probiotic supplementation also improved muscle glucose uptake, as measured using Positron Emission Tomography (PET) analysis. In conclusion, these data provide a proof of concept that probiotics, as a dietary intervention in AIP, induce relevant changes in intestinal bacteria composition and improve glucose uptake and muscular energy utilization. Probiotics may offer a safe, efficient, and cost-effective option to manage people with insulin resistance associated with AIP.This research was supported in part by grants from the Spanish Institute of Health Carlos III (FIS) cofunded by the European Union (ERDF/ESF, “A way to make Europe”/“Investing in your future” (grant number PI21/00546) and the Spanish Fundación Mutua Madrileña de Investigación Médica

The effect of thiamine-coating nanoparticles on their biodistribution and fate following oral administration

Thiamine-coated nanoparticles were prepared by two different preparative methods and evaluated to compare their mucus-penetrating properties and fate in vivo. The first method of preparation consisted of surface modification of freshly poly(anhydride) nanoparticles (NP) by simple incubation with thiamine (T-NPA). The second procedure focused on the preparation and characterization of a new polymeric conjugate between the poly(anhydride) backbone and thiamine prior the nanoparticle formation (T-NPB). The resulting nanoparticles displayed comparable sizes (about 200 nm) and slightly negative surface charges. For T-NPA, the amount of thiamine associated to the surface of the nanoparticles was 15 µg/mg. For in vivo studies, nanoparticles were labeled with either 99mTc or Lumogen® Red. T-NPA and T-NPB moved faster from the stomach to the small intestine than naked nanoparticles. Two hours post-administration, for T-NPA and T-NPB, more than 30% of the given dose was found in close contact with the intestinal mucosa, compared with a 13.5% for NP. Interestingly, both types of thiamine-coated nanoparticles showed a greater ability to cross the mucus layer and interact with the surface of the intestinal epithelium than NP, which remained adhered in the mucus layer. Four hours post-administration, around 35% of T-NPA and T-NPB were localized in the ileum of animals. Overall, both preparative processes yielded thiamine decorated carriers with similar physico-chemical and biodistribution properties, increasing the versatility of these nanocarriers as oral delivery systems for a number of biologically active compounds

A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer

BackgroundHarnessing the anti-tumor immune system response by targeting the program cell death protein (PD-1) and program cell death ligand protein (PD-L1) axis has been a major breakthrough in non-small cell lung cancer (NSCLC) therapy. Nonetheless, conventional imaging tools cannot accurately assess response in immunotherapy-treated patients. Using a lung cancer syngeneic mouse model responder to immunotherapy, we aimed to demonstrate that [89Zr]-anti-PD-1 immuno-PET is a safe and feasible imaging modality to assess the response to PD-1/PD-L1 blockade in NSCLC.Materials and methodsA syngeneic mouse model responder to anti-PD-1 therapy was used. Tumor growth and response to PD-1 blockade were monitored by conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) PET scans. Additionally, tumor lymphocyte infiltration was analyzed by the use of an [89Zr]-labeled anti-PD-1 antibody and measured as 89Zr tumor uptake.ResultsConventional [18F]-FDG-PET scans failed to detect the antitumor activity exerted by anti-PD-1 therapy. However, [89Zr]-anti-PD-1 uptake was substantially higher in mice that responded to PD-1 blockade. The analysis of tumor-infiltrating immune cell populations and interleukins demonstrated an increased anti-tumor effect elicited by activation of effector immune cells in PD-1-responder mice. Interestingly, a positive correlation between [89Zr]-anti-PD-1 uptake and the proportion of tumor-infiltrating lymphocytes (TILs) was found (Cor = 0.8; p = 0.001).ConclusionOur data may support the clinical implementation of immuno-PET as a promising novel imaging tool to predict and assess the response of PD-1/PD-L1 inhibitors in patients with NSCLC