π‐Extended Donor–Acceptor Porphyrins and Metalloporphyrins for Antimicrobial Photodynamic Inactivation

Free base, zinc and palladium π‐extended porphyrins containing fused naphthalenediamide units were employed as photosensitizers in antimicrobial photodynamic therapy (aPDT). Their efficacy, assessed by photophysical and in vitro photobiological studies on Gram‐positive bacteria, was found to depend on metal coordination, showing a dramatic enhancement of photosensitizing activity for the palladium complex

Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

Social Transfer of Pathogenic Fungus Promotes Active Immunisation in Ant Colonies

Social contact with fungus-exposed ants leads to pathogen transfer to healthy nest-mates, causing low-level infections. These micro-infections promote pathogen-specific immune gene expression and protective immunization of nest-mates

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

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Abstract: Melanin formation in pigmented melanoma cells is considered as a target for the tumor therapy. The evaluation of potential correlation between melanin structure and the tumor type could be also of diagnostic and prognostic importance. One of the major problems in structural investigations of natural melanins is the lack of appropriate methods, which allow isolation of pure intact pigment. In this study the thermochemolysis technique was used to assess the purification grade of melanin isolated from the human melanoma malignum cells by two different enzymatic methods. Melanin samples were thermally degraded in the presence of tetramethylammonium hydroxide and the thermochemolysis products were analyzed by gas chromatography/mass spectrometry (GC/MS). Compounds of lipid origin, especially fatty acid methyl esters and aliphatic and cyclic hydrocarbons, were predominant among pyrolysis products of melanin isolated from the tumor cells by method I. In contrast, during thermochemolysis of the pigment sample isolated by the method II, mainly eumelanin markers (pyrrole and its methyl derivatives, toluene, styrene, phenol, benzyl nitrile and indole) were formed. The comparison of pyrolysis profiles of the analyzed samples indicate that method II is more efficient for melanoma pigment purification

π‐Extended Donor–Acceptor Porphyrins and Metalloporphyrins for Antimicrobial Photodynamic Inactivation

Free base, zinc and palladium π‐extended porphyrins containing fused naphthalenediamide units were employed as photosensitizers in antimicrobial photodynamic therapy (aPDT). Their efficacy, assessed by photophysical and in vitro photobiological studies on Gram‐positive bacteria, was found to depend on metal coordination, showing a dramatic enhancement of photosensitizing activity for the palladium complex