Migraine-like headaches associated with nickel allergy requiring removal of atrial septal defect closure device

There is a deficit of literature regarding the association between nickel allergy–induced symptoms and implanted devices. This report describes a case of nickel allergy causing debilitating migraine-like symptoms, failing to resolve with medical therapy, requiring surgical removal of the device and repair of the defect.     

Chemosensitization of murine fibrosarcoma cells to drugs affected by the multidrug resistance phenotype by the antidepressant trazodone - an experimental-model for the reversal of intrinsic drug-resistance

A variety of resistance phenotypes to cytotoxic agents in bacteria, protozoa parasites and mammalian cells are mediated by evolutionarily conserved proteins of the mdr family. The finding that chloroquine resistance in the malarial parasite, Plasmodium falciparum, that is mediated by an mdr-1 gene product can be circumvented by tricyclic antidepressant drugs has stimulated the present study to assess whether this class of agents might also modulate the multidrug resistance (MDR) phenotype(s) in mammalian tumor cells. The possible chemosensitizing effects of nine antidepressant drugs have been tested against the UV-2237M murine fibrosarcoma line and its MDR variant. At nontoxic concentrations all nine antidepressants markedly enhanced the cytotoxicity of ADR against the parental cells but were much less effective against the MDR cells. The most active antidepressant, trazodone, also enhanced the cytotoxicities of vinblastine and vincristine, but not those of actinomycin D, mitomycin C, or 5-fluorouracil. The parental cells treated with trazodone exhibited an increased accumulation of intracellular ADR, but lacked detectable alterations in the expression and drug-binding activity of plasma membrane P-glycoprotein, and trazodone did not affect the activities of isolated protein kinase C and calmodulin. These data suggest that the antidepressant drug trazodone may be useful in the reversal of the intrinsic drug resistance of tumor cells that express low levels of P-glycoprotein.     

Mental retardation and sentences for murder: comparison of two recent court cases

Several states and the United States have laws that exempt persons who have mental retardation from the death penalty and other severe sentences. Two recent murder cases in Indiana, which has such a law, illustrate some of the problems in applying it. The characteristics of the two defendants were quite similar, but one defendant was found to have mental retardation and was exempted from the death penalty and the other was not. The disparity was attributed to differences in the assessment of adaptive behavior and to general stereotypes of people who have mental retardation. Equal application of sentencing limitation laws requires greater involvement of professionals with specialized training and experience in mental retardation.     

The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination

Background The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies.Methods Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification. The cohort included 22 HPV-positive (primarily HPV-16) and 18 HPV-negative samples. A benign reference dataset comprised of the HLA ligandomes of benign haematological and tissue datasets was used to identify tumour-associated antigens.Results MS analysis led to the identification of naturally HLA-presented peptides in OPSCC tumour tissue. In total, 22,769 peptides from 9485 source proteins were detected on HLA class I. For HLA class II, 15,203 peptides from 4634 source proteins were discovered. By comparative profiling against the benign HLA ligandomic datasets, 29 OPSCC-associated HLA class I ligands covering 11 different HLA allotypes and nine HLA class II ligands were selected to create a peptide warehouse.Conclusion Tumour-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi)personalised strategies. Subject terms: Tumour immunology, Translational research     

Retinal venous occlusion following COVID-19 vaccination: Report of a case after third dose and review of the literature

A 28-year-old, healthy male presented with blurring of vision in the right eye following third dose of the AstraZeneca/COVISHIELD vaccine. Further examination revealed ischemic central retinal vein occlusion, and subsequent laboratory investigations were inconclusive for his eye disease. He responded to pulse corticosteroid and tapering doses of oral corticosteroids without requiring any intra-vitreal injection. Twelve articles were identified with the help of a PubMed literature search, and a short review of these patients was performed. Retinal vein occlusion can occur because of inflammation-induced thrombosis after coronavirus disease 2019 vaccination and may respond to anti-inflammatory therapy.