Histone acetylome-wide associations in immune cells from individuals with active Mycobacterium tuberculosis infection

Host cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here we describe a histone acetylome-wide association study (HAWAS) of an infectious disease, on the basis of genome-wide H3K27 acetylation profiling of peripheral blood granulocytes and monocytes from persons with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Singapore Chinese discovery cohort (n = 46), which were validated in a subsequent multi-ethnic Singapore cohort (n = 29), as well as a longitudinal cohort from South Africa (n = 26), thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulates apoptosis and promotes Mtb clearance in vitro. We performed histone acetylation quantitative trait locus (haQTL) analysis on the dataset and identified 69 candidate causal variants for immune phenotypes among granulocyte haQTLs and 83 among monocyte haQTLs. Our study provides proof-of-principle for HAWAS to infer mechanisms of host response to pathogens

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Standardization and validation of a cytometric bead assay to assess antibodies to multiple <it>Plasmodium falciparum</it> recombinant antigens

<p>Abstract</p> <p>Background</p> <p>Multiplex cytometric bead assay (CBA) have a number of advantages over ELISA for antibody testing, but little information is available on standardization and validation of antibody CBA to multiple <it>Plasmodium falciparum</it> antigens. The present study was set to determine optimal parameters for multiplex testing of antibodies to <it>P. falciparum</it> antigens, and to compare results of multiplex CBA to ELISA.</p> <p>Methods</p> <p>Antibodies to ten recombinant <it>P. falciparum</it> antigens were measured by CBA and ELISA in samples from 30 individuals from a malaria endemic area of Kenya and compared to known positive and negative control plasma samples. Optimal antigen amounts, monoplex <it>vs</it> multiplex testing, plasma dilution, optimal buffer, number of beads required were assessed for CBA testing, and results from CBA vs. ELISA testing were compared.</p> <p>Results</p> <p>Optimal amounts for CBA antibody testing differed according to antigen. Results for monoplex CBA testing correlated strongly with multiplex testing for all antigens (<it>r</it> = 0.88-0.99, <it>P</it> values from <0.0001 - 0.004), and antibodies to variants of the same antigen were accurately distinguished within a multiplex reaction. Plasma dilutions of 1:100 or 1:200 were optimal for all antigens for CBA testing. Plasma diluted in a buffer containing 0.05% sodium azide, 0.5% polyvinylalcohol, and 0.8% polyvinylpyrrolidone had the lowest background activity. CBA median fluorescence intensity (MFI) values with 1,000 antigen-conjugated beads/well did not differ significantly from MFI with 5,000 beads/well. CBA and ELISA results correlated well for all antigens except apical membrane antigen-1 (AMA-1). CBA testing produced a greater range of values in samples from malaria endemic areas and less background reactivity for blank samples than ELISA.</p> <p>Conclusion</p> <p>With optimization, CBA may be the preferred method of testing for antibodies to <it>P. falciparum</it> antigens, as CBA can test for antibodies to multiple recombinant antigens from a single plasma sample and produces a greater range of values in positive samples and lower background readings for blank samples than ELISA.</p

Neurocysticercosos in South-Central America and the Indian Subcontinent: a comparative evaluation

Neurocysticercosis is an important public health problem in South-Central America and South Asia. A review of the differences in epidemiological and clinical attributes of cysticercosis and taeniasis in South Central America and India, respectively, is undertaken in the present communication. Intestinal taeniasis is hyperendemic in several American countries. In comparison, the prevalence of Taenia solium infestation is lower in India. The clinical manifestations in several American neurocysticercosis series comprise epilepsy, intracranial hypertension and meningeal - racemose cysticercosis, in roughly equal proportions. An overwhelming majority of the Indian subjects present with seizures. The commonest pathological substrate of the disorder in Indian patients is the solitary parenchymal degenerating cyst. The reasons for the predominance of solitary forms in India, and of multilesional forms in South Central America are discussed. The magnitude of Taenia solium infestation and the frequency of pork consumption in a given population appear to influence the quantum of cyst load in affected individuals