Linkage Specific Fucosylation of Alpha-1-Antitrypsin in Liver Cirrhosis and Cancer Patients: Implications for a Biomarker of Hepatocellular Carcinoma

We previously reported increased levels of protein-linked fucosylation with the development of liver cancer and identified many of the proteins containing the altered glycan structures. One such protein is alpha-1-antitrypsin (A1AT). To advance these studies, we performed N-linked glycan analysis on the five major isoforms of A1AT and completed a comprehensive study of the glycosylation of A1AT found in healthy controls, patients with hepatitis C- (HCV) induced liver cirrhosis, and in patients infected with HCV with a diagnosis of hepatocellular carcinoma (HCC).Patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan-containing outer arm (alpha-1,3) fucosylation. Increases in core (alpha-1,6) fucosylation were observed only on A1AT from patients with cancer. We performed a lectin fluorophore-linked immunosorbent assay using Aleuria Aurantia lectin (AAL), specific for core and outer arm fucosylation in over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC with a sensitivity of 70% and a specificity of 86%, which was greater than that observed with the current marker of HCC, alpha-fetoprotein. Glycosylation analysis of the false positives was performed; results indicated that these patients had increases in outer arm fucosylation but not in core fucosylation, suggesting that core fucosylation is cancer specific.This report details the stepwise change in the glycosylation of A1AT with the progression from liver cirrhosis to cancer and identifies core fucosylation on A1AT as an HCC specific modification

Globally, songs and instrumental melodies are slower and higher and use more stable pitches than speech: A Registered Report

Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness. Exploratory analyses suggest that features vary along a “musi-linguistic” continuum when including instrumental melodies and recited lyrics. Our study provides strong empirical evidence of cross-cultural regularities in music and speech

Azathioprine and Infliximab: Monotherapy or Combination Therapy in the Treatment of Crohn's Disease

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract often resulting in complications resulting in decreased quality of life. Several classes of medications are available to clinicians including mesalamine, budesonide, systemic corticosteroids, thiopurine derivatives, and monoclonal antibodies which target tumor necrosis factor (TNF). Guidelines generally recommend reserving TNF-antagonists for patients who have failed other first-line therapies; however, emerging data suggests there may be some benefit in combining TNF-antagonists, specifically infliximab, with azathioprine. The purpose of this review is to compare the benefits and risks of combination therapy, and identify patients who may benefit most from this approach

Malaria causes long-term effects on markers of iron status in children: a critical assessment of existing clinical and epidemiological tools

Abstract Background Most epidemiological studies on the interplay between iron deficiency and malaria risk classify individuals as iron-deficient or iron-replete based on inflammation-dependent iron markers and adjustment for inflammation by using C-reactive protein (CRP) or α-1-acid glycoprotein (AGP). The validity of this approach and the usefulness of fibroblast growth factor 23 (FGF23) as a proposed inflammation-independent iron marker were tested. Methods Conventional iron markers and FGF23 were measured in children with acute falciparum malaria and after 1, 2, 4, and 6 weeks. Children, who were transfused or received iron supplementation in the follow-up period, were excluded, and iron stores were considered to be stable throughout. Ferritin levels 6 weeks after admission were used as a reference for admission iron status and compared with iron markers at different time points. Results There were long-term perturbations in iron markers during convalescence from acute malaria. None of the tested iron parameters, including FGF23, were independent of inflammation. CRP and AGP normalized faster than ferritin after malaria episodes. Conclusion Malaria may bias epidemiological studies based on inflammation-dependent iron markers. Better markers of iron status during and after inflammation are needed in order to test strategies for iron supplementation in populations at risk of malaria

Journal of African Christian Biography: v. 8, no. 3 (July 2023) A quaterly publication of the Dictionary of African Christian Biography (www.DACB.org)

[Throughout African Christian history, catechists and evangelists have carried out the lions’ share of the work of mission. Catechists were generally served in Roman Catholic and Anglican churches as lay (non ordained) ministers and indigenous teachers. Their role was to instruct inquirers or new believers in the Christian faith. In Protestant churches, evangelists played an important role in outreach, often preaching in public places to draw people to the church. Their goal was to inspire their listeners to convert to Christianity.1 Many churches had male and female evangelists although the women were often not recognized and remunerated for their service, as the men were. Both catechists and evangelists traveled frequently, moving from village to village as the needs arose. This issue showcases the biographies of three exceptional African missionaries. Fr. Cosmas Sarbah, PhD, writes the story of his grandfather, John E. Sarbah, a catechist in the Roman Catholic Church of Ghana, who performed almost all the work of a parish priest for countless parishes throughout his region filling in where there was a shortage of priests and of European missionaries. Kimeze Teketwe presents the exciting story of Sembera K. Mackay, the first Anglican convert and the first to request baptism in nineteenth century Uganda. Sembera had such an impact through his lifelong ministry as a catechist that the author theorizes that his name might have been chosen to express the Luganda concept of Christian eucharist (communion) – Oku-sembera. Professor Dickson Nkonge Kagema gives us the story of Jerusha Kanyua, an extraordinary woman who ministered as an evangelist, a teacher, a midwife, a prayer warrior, and a prophetess, leaving a lasting legacy in her home region in Kenya.