Leishmania infantum infection after visiting southern Spain in patients on biological treatment; an observational, longitudinal, cohort study

Background: Reports of leishmaniasis in immunosuppressed patients after visiting the Mediterranean Basin are becoming increasingly common. Still, awareness of the risk of infection and its clinical manifestations may be insufficient among healthcare professionals in the travellers' home countries. Methods: This observational, longitudinal study included 47 patients from Sweden with rheumatic disease and ongoing immunomodulatory treatment, who visited a rehabilitation centre in southern Spain where leishmaniasis is endemic. Patients were evaluated for clinical signs of leishmaniasis at baseline and after three years. Patients with leishmaniasis were followed for 4-5 years. The treatment outcome was assessed by clinical evaluation and determination of the cell-mediated immunological response to Leishmania by a whole blood cytokine release assay. Results: Seven patients (15%) were diagnosed with leishmaniasis. The median time from exposure to the onset of symptoms was 3 [1-17] months. The median delay between the onset of symptoms and treatment start was 9 [1-12] months. All patients with leishmaniasis responded well to treatment. Only one patient had a relapse, which occurred within the first year. Conclusion: Healthcare professionals need to be aware of the increased risk of leishmaniasis for travellers who are immunosuppressed. Knowledge of the symptoms is crucial for a timely diagnosis and early treatment.S

Early vaccinations are not risk factors for celiac disease.

OBJECTIVES: To investigate if changes in the national Swedish vaccination program coincided with changes in the celiac disease (CD) incidence rate in infants (ie, the Swedish CD Epidemic), and to assess the potential association between these vaccinations and CD risk. METHODS: All studies were based on the National Swedish Childhood Celiac Disease Register. Using an ecological approach, we plotted changes over time in the national vaccination program in the graph displaying CD incidence rate. A population-based incident case-referent study of invited infants was performed. Exposure information was received through a questionnaire and child health clinic records. Vaccines explored were diphtheria/tetanus, pertussis (acellular), polio (inactivated), Haemophilus influenzae type b (conjugated), measles/mumps/rubella, and live attenuated bacillus Calmette-Guérin (BCG) in children with increased tuberculosis risk. Findings were subjected to a birth cohort analysis. RESULTS: Introduction of pertussis vaccine coincided in time with decreasing CD incidence rates. In the infant case-referent study, however, neither vaccination against pertussis (odds ratio 0.91; 95% confidence interval 0.60-1.4), nor against Haemophilus influenzae type b or measles/mumps/rubella was associated with CD. Coverage for the diphtheria/tetanus and polio vaccines was 99%. BCG was associated with reduced risk for CD (adjusted odds ratio 0.54; 95% confidence interval 0.31-0.94). Discontinuation of general BCG vaccination did not affect the cumulative incidence of CD at age 15 years. CONCLUSIONS: Early vaccinations within the national Swedish program were not associated with CD risk, nor could changes in the program explain the Swedish epidemic. A protective effect by BCG was suggested, which could be subject to further studies

Photochemically induced isomerisation in ruthenium polypyridyl complexes

The synthesis and characterisation of a series of ruthenium polypyridyl complexes containing pyridyltriazole ligands in different coordination modes are described. The electrochemical and electronic properties of the compounds are reported and discussed with respect to the coordination mode of the pyridyltriazole ligand. Upon photolysis of the complex containing the 1-methyl-3-(pyridin-2-yl)-1,2,4-triazole ligand irreversible ligand isomerisation is observed

Detrimental NFKB1 missense variants affecting the Rel-homology domain of p105/p50

Most of the currently known heterozygous pathogenic NFKB1 (Nuclear factor kappa B subunit 1) variants comprise deleterious defects such as severe truncations, internal deletions, and frameshift variants. Collectively, these represent the most frequent monogenic cause of common variable immunodeficiency (CVID) identified so far. NFKB1 encodes the transcription factor precursor p105 which undergoes limited proteasomal processing of its C-terminal half to generate the mature NF-kappa B subunit p50. Whereas p105/p50 haploinsufficiency due to devastating genetic damages and protein loss is a well-known disease mechanism, the pathogenic significance of numerous NFKB1 missense variants still remains uncertain and/or unexplored, due to the unavailability of accurate test procedures to confirm causality. In this study we functionally characterized 47 distinct missense variants residing within the N-terminal domains, thus affecting both proteins, the p105 precursor and the processed p50. Following transient overexpression of EGFP-fused mutant p105 and p50 in HEK293T cells, we used fluorescence microscopy, Western blotting, electrophoretic mobility shift assays (EMSA), and reporter assays to analyze their effects on subcellular localization, protein stability and precursor processing, DNA binding, and on the RelA-dependent target promoter activation, respectively. We found nine missense variants to cause harmful damage with intensified protein decay, while two variants left protein stability unaffected but caused a loss of the DNA-binding activity. Seven of the analyzed single amino acid changes caused ambiguous protein defects and four variants were associated with only minor adverse effects. For 25 variants, test results were indistinguishable from those of the wildtype controls, hence, their pathogenic impact remained elusive. In summary, we show that pathogenic missense variants affecting the Rel-homology domain may cause protein-decaying defects, thus resembling the disease-mechanisms of p105/p50 haploinsufficiency or may cause DNA-binding deficiency. However, rare variants (with a population frequency of less than 0.01%) with minor abnormalities or with neutral tests should still be considered as potentially pathogenic, until suitable tests have approved them being benign.Peer reviewe

Strategies for Switching the Mechanism of Proton-Coupled Electron Transfer Reactions Illustrated by Mechanistic Zone Diagrams

The mechanism under which proton-coupled electron transfer (PCET) occurs has great consequences for applications in catalysis. However, determination and tuning of the PCET mechanism is often non-trivial. Here, we apply mechanistic zone diagrams to illustrate the competition between PCET-mechanisms in the oxidation of 4-Methoxyphenol by Ru(bpy)33+-derivatives in the presence of substituted pyridine bases. These diagrams show the dominating mechanism as a function of driving force for electron and proton transfer (ΔG0ET and ΔG0PT) respectively [Tyburski et al., J. Am. Chem. Soc., 2021, 143, 560]. Within this framework, we demonstrate strategies for mechanistic tuning, namely balancing of ΔG0ET and ΔG0PT, steric hindrance of the proton-transfer coordinate, and isotope substitution. For cases when strong oxidants are used, substitution of protons for deuterons leads to a switch from concerted electron-proton transfer (CEPT) to an electron transfer limited (ETPTlim) mechanism. We thereby, for the first time, provide direct experimental evidence, that vibronic coupling affects the switching point between CEPT and ETPTlim, i.e. at what driving force one or the other mechanism starts dominating. Implications for solar fuels catalysis are discussed

Photoredox Catalysis Using Heterogenized Iridium Complexes

Heterogenized photoredox catalysts provide a path to generating chemicals in an environmentally friendly way, with facile reuse of catalysts in batch or continuous processes. In this study, heterogenized iridium complexes as photoredox catalysts were assembled via covalent attachment to three metal oxide surfaces (ITO, ZrO2, Al2O3) either in the form of thin films or nanopowders and tested as photoredox catalysts for reductive dehalogenation of bromoacetophenone to acetophenone. All catalysts produced acetophenone with high conversions and yields. The fastest reactions were complete in fifteen minutes under mild conditions using Al2O3 surfaces, which provided the most robust and reusable supports. The catalytic performance was compared on both nanopowder and thin film supports, showing that both constructs could be used for photoredox catalysis. The nanopowder-based catalysts resulted in faster and more efficient catalysis, while the thin film-immobilized catalysts were more robust and easily reused. Importantly, the thin film constructs show promise for future photoelectrochemical and electrochemical photoredox setups. Finally, all catalysts could be reused 2-3 times, performing at least 1000 turnovers with Al2O3 supports, highlighting that heterogenized catalysts can perform photoredox catalysis in an environmentally friendly fashion. <br /

Mechanistic Insights into the Photocatalytic Hydrogen Production of Y5 and Y6 Nanoparticles

Utilization of solarenergy in organic semiconductorsrelies oncomplicated photophysical processes due to the strong electron-holeinteractions. To gain a better understanding of these processes andtheir effect on the photocatalytic performance of non-fullerene acceptors(NFAs) within nanoparticles (NPs), we compared the excited-state dynamicsand photocatalytic hydrogen production activity of two NFA-based NPs,Y5 and Y6. Our results show that under LED light irradiation, Y5 NPsexhibit 14 times better hydrogen production activity than Y6 NPs.The hydrogen production activity was also evaluated under Xenon lightirradiation (AM1.5G, 100 mW &amp; BULL;cm(-2)) for Y5 NPs,yielding 410 mmol/g after 24 h. Time-resolved spectroscopy experimentsrevealed a longer triplet lifetime for Y5 compared to Y6 NPs, andthe lifetime was reduced upon addition of the electron donor ascorbate.This suggests the involvement of the triplet state in reductive quenchingand better hydrogen evolution reaction performance for Y5 NPs. Thegood agreement between fluorescence and triplet lifetimes observedfor Y5 NPs was attributed to reverse intersystem crossing, which repopulatesthe excited singlet state through thermally activated delayed fluorescence(TADF). The absence of TADF in Y6 NPs could limit its efficiency forhydrogen evolution reaction, in addition to the intrinsically shortertriplet lifetime and reduction potential difference, making it animportant factor to consider in Y series-based NPs