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Highlights d Incorporation of iodine or sulfur into rhodamine dyes increases 1 O 2 quantum yield d Rhodamine photosensitizers are compatible with live-celllabeling strategies d Generating 1 O 2 allows photoablation of entire cells in culture or in vivo

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We sought to correct the multiple organ dysfunction of the F508del CF-causing mutation using systemic delivery of peptide nucleic acid gene editing technology mediated by biocompatible polymeric nanoparticles. We confirmed phenotypic and genotypic modification in vitro in primary nasal epithelial cells from F508del mice grown at air-liquid interface and in vivo in F508del mice following intravenous delivery. In vivo treatment resulted in a partial gain of CFTR function in epithelia as measured by in situ potential differences and Ussing chamber assays and correction of CFTR in both airway and GI tissues with no off-target effects above background. Our studies demonstrate that systemic gene editing is possible, and more specifically that intravenous delivery of PNA NPs designed to correct CF-causing mutations is a viable option to ameliorate CF in multiple affected organs.

Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves destruction of both donor and recipient red blood cells (RBCs). As the epidemiology and underlying pathophysiology have yet to be definitively elucidated, recognition can be challenging. We systematically reviewed PubMed and EMBASE to identify all cases of post-transfusion hyperhaemolysis and characterized the epidemiological, clinical and immunohaematological characteristics and treatments of HHS. We identified 51 patients (33 females and 18 males), including 31 patients with SCD (HbSS, HbSC and HbS/β-thalassaemia). The median haemoglobin nadir (3.9 g/dL) occurred a median of 10 days post-transfusion. 32.6% and 45.7% of patients had a negative indirect anti-globulin test and a negative direct anti-globulin test, respectively. The most common therapies included corticosteroids and intravenous immune globulin. 66.0% of patients received ≥1 supportive transfusion, which was associated with a longer median hospital stay/time to recovery (23 days vs. 15 days; p = 0.015) compared to no supportive transfusion. These findings illustrate that HHS that often results in marked anaemia 10 days post-transfusion is not restricted to patients with haemoglobinopathies, and additional transfused RBCs may be associated with a longer time-to-recovery.

Background: Warm autoimmune hemolytic anemia (WAIHA) is characterized by the development of autoantibodies that react with red blood cells (RBCs) optimally at physiologic temperature, classically resulting in a positive direct antiglobulin test (DAT) for IgG and a panreactive eluate. Babesiosis has been described as a potentiator of WAIHA, and all cases have shown classic blood bank findings. Only rare reports have described autoantibodies, both secondary to babesiosis and overall, with specificity for Kidd antigens.Methods: Antibody detection and identification were performed using IgGspecific column agglutination technology. Jk a antigen phenotyping was assessed using monoclonal reagents and genotypic analysis was performed at an immunohematology reference laboratory. DATs were performed via standard tube methods. The elution was performed using the ELUclear glycine acid red cell elution kit. Results: We report a case of WAIHA induced by Babesia microti infection with an autoantibody with Jk a specificity, originally believed to be a delayed hemolytic transfusion reaction, given the detection of an RBC antibody in close proximity to numerous RBC transfusions. Determination of autoantibody status with anti-Jk a -like reactivity was only confirmed after Kidd antigen genotyping predicted expression of the Jk a antigen.Discussion: Healthcare providers should be cognizant of the potential for babesiosis-induced WAIHA, particularly in individuals who continue to hemolyze despite undetectable parasitemia. Furthermore, this case highlights the possibility for warm autoantibodies to demonstrate Kidd antigen specificity. Though Kidd antigen variants are rare, antigen genotyping may be beneficial, particularly in the context of recent RBC transfusions, which typically preclude accurate serological phenotypic assessment.

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