Global priority multidrug-resistant pathogens do not resist photodynamic therapy.

Microbial drug-resistance demands immediate implementation of novel therapeutic strategies. Antimicrobial photodynamic therapy (aPDT) combines the administration of a photosensitizer (PS) compound with low-irradiance light to induce photochemical reactions that yield reactive oxygen species (ROS). Since ROS react with nearly all biomolecules, aPDT offers a powerful multitarget method to avoid selection of drug-resistant strains. In this study, we assayed photodynamic inactivation under a standardized method, combining methylene blue (MB) as PS and red light, against global priority pathogens. The species tested include Acinetobacter baumannii, Klebsiella aerogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecium, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and Cryptococcus neoformans. Our strain collection presents resistance to all tested antimicrobials (>50). All drug-resistant strains were compared to their drug-sensitive counterparts. Regardless of resistance phenotype, MB-aPDT presented species-specific dose-response kinetics. More than 5log10 reduction was observed within less than 75 s of illumination for A. baumannii, E. coli, E. faecium, E. faecalis and S. aureus and within less than 7 min for K. aerogenes, K. pneumoniae, P. aeruginosa, C. albicans and C. neoformans. No signs of correlations in between drug-resistance profiles and aPDT sensitivity were observed. Therefore, MB-aPDT can provide effective therapeutic protocols for a very broad spectrum of pathogens. Hence, we believe that this study represents a very important step to bring aPDT closer to implementation into mainstream medical practices

Serotonin transporter polymorphism moderates the effects of caregiver intrusiveness on ADHD symptoms among institutionalized preschoolers

Research consistently chronicles a variety of mental health difficulties that plague institutionally reared children, including attention-deficit/hyperactivity disorder (ADHD), even if not all institutionalized children evince such problems. In seeking to extend work in this area, this research on gene × environment (GXE) interplay investigated whether the effect of the quality of institutional care-most notably, caregiver intrusiveness-on ADHD symptoms is moderated by the serotonin transporter (5-HTTLPR) polymorphism. One hundred and twenty-seven institutionalized preschoolers were evaluated using the Child Behavior Checklist. Caregiver-rated attention problems and hyperactivity were unrelated to both 5-HTTLPR polymorphism and caregiver intrusiveness. A significant GXE effect, independent of age at placement or duration of institutionalization, emerged, however, consistent with the differential-susceptibility hypothesis: s/s homozygotes manifest the most and least ADHD symptoms when they experienced, respectively, more and less intrusive caregiving. These results provide new insight into the reasons why some institutionalized children, but not others, exhibit ADHD symptoms.This study was conducted within the Psychology Research Centre, University of Minho, and partially supported by the Portuguese Foundation for Science and Technology (PTDC/ PSI-PCL/101506/2008 and PTDC/PSI-PCL/116897/2010; also grant SFRH/BPD/100994/2014 assigned to the first author) and by the Portuguese Ministry of Education and Science through national funds and when applicable co-financed by FEDER under the PT2020 Partnership Agreement (UID/PSI/01662/2013). This study was also partially supported by grant 13/06 from Fundação BIAL. The authors are very grateful to the students who helped in data collection. Special thanks go to the children, caregivers, and other institutional staff who participated in the study.info:eu-repo/semantics/publishedVersio