Publications by authors named "D W Denno"

Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTDs), including coronavirus disease 2019 (COVID-19), but there are minimal data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. In this study, we used histology and high-dimensional imaging to characterize fatal lung disease in Malawian adults with (n = 9) and without (n = 7) COVID-19, and we generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved COVID-19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in US, European and Asian cohorts, by type I/III interferon (IFN) responses, particularly in blood-derived monocytes, and in the Malawian cohort, by response to IFN-γ in lung-resident macrophages.

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Background: Environmental Enteric Dysfunction (EED) is an acquired disorder of asymptomatic altered gut function, the etiology of which is unknown. EED is postulated to be a major contributor to growth faltering in early childhood in regions where early-life enteropathogenic carriage is prevalent. Few studies have examined the critical organ (the upper small bowel) with enteropathogens in the evolution of small bowel disease.

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Background: Validated biomarkers could catalyze environmental enteric dysfunction (EED) research.

Objectives: Leveraging an EED histology scoring system, this multicountry analysis examined biomarker associations with duodenal histology features among children with EED. We also examined differences in 2-h compared with 1-h urine collections in the lactulose rhamnose (LR) dual sugar test.

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Background: Environmental enteric dysfunction (EED) is a precursor of growth faltering in children living in impoverished conditions who are frequently exposed to environmental toxins and enteropathogens, leading to small bowel inflammatory, malabsorptive, and permeability derangements and low-grade chronic systemic inflammation.

Objectives: We explored the association between anthropometrics and duodenal histologic features of EED among children from 3 lower middle-income country centers.

Methods: In this cross-sectional study, Pakistani children (n = 63) with wasting, Bangladesh children (n = 116) with stunting or at risk for stunting (height-for-age Z score [HAZ] <-1 but ≥-2), and Zambian children (n = 108) with wasting or stunting received nutritional intervention.

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Article Synopsis
  • - Environmental enteric dysfunction (EED) is a condition that leads to inflammation in the small intestine, impacting childhood growth and neurodevelopment, but has been overlooked until recently.
  • - The EEDBI Consortium was formed in 2016 to study EED through biopsy data from children in Bangladesh, Pakistan, and Zambia, while also comparing them to children in the U.S. undergoing endoscopy for other reasons.
  • - The initiative aims to coordinate research efforts, allowing researchers to analyze EED-related tissue and associated factors like histology and biomarkers across multiple studies, all with the goal of better understanding this debilitating condition.
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