Margret M. and Paul B. Baltes Award Lecture: Optimism and Health: Resource or Delusion?

The lecture will be given by the 2020 Baltes Award recipient, William Chopik, PhD, of Michigan State University. The recipient of the 2021 Baltes Award is Laura B. Zahodne, PhD, of the University of Michigan. The Margret M. and Paul B. Baltes Foundation Award in Behavioral and Social Gerontology recognizes outstanding early-career contributions in behavioral and social gerontology. The award is generously funded by the Margret M. and Paul B. Baltes Foundation.

Immuno-fibrotic drivers of impaired lung function in post-COVID-19 syndrome

ABSTRACTIntroductionSubjects recovering from COVID-19 frequently experience persistent respiratory ailments; however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity.MethodsWe performed a prospective cohort study of subjects with persistent symptoms after recovering from acute COVID-19 illness, collecting clinical data, pulmonary function tests, and blood. Plasma samples were used for multiplex profiling of circulating factors associated with inflammation, metabolism, angiogenesis, and fibrosis.ResultsSixty-one subjects were enrolled across two academic medical centers at a median of 9 weeks (interquartile range 6-10) after COVID-19 illness: n=13 subjects (21%) mild/non-hospitalized, n=30 (49%) hospitalized/non-critical, and n=18 subjects (30%) hospitalized/intensive care (“ICU”). Fifty-three subjects (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P<0.05), but did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered subjects by past COVID-19 severity. Lipocalin 2 (LCN2), matrix metalloproteinase-7 (MMP-7), and hepatocyte growth factor (HGF) identified by the model were significantly higher in the ICU group (P<0.05) and inversely correlated with FVC and DLCO (P<0.05).ConclusionsSubjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets.FundingThe study was funded in part by the NHLBI (K08HL130557 to BDK and R01HL142818 to HJC), the DeLuca Foundation Award (AP), a donation from Jack Levin to the Benign Hematology Program at Yale, and Divisional/Departmental funds from Duke University.

Margret M. and Paul B. Baltes Award

The lecture will be given by the2019 Baltes Award recipient, Allison Bielak, PhD, FGSA, of Colorado State University. The recipient of the2020 Baltes Award is William J. Chopik, PhD. The Margret M. and Paul B. Baltes Foundation Award in Behavioral and Social Gerontology recognizes outstanding early-career contributions in behavioral and social gerontology. The award is generously funded by the Margret M. and Paul B. Baltes Foundation.

Differences in the Concentration and Composition of Human Milk Components Are Related to Variation in Milk and Infant Fecal Microbiomes

Objectives Profiles of human milk oligosaccharides (HMO) and milk/infant fecal microbiota vary globally. However, associations between and among HMO, other milk-borne factors (e.g., lactose, protein), and milk/infant fecal microbiomes have not been well-investigated. Here we tested the hypothesis that variations in milk lactose, protein, and HMO concentrations are associated with variations in the structure of milk and infant fecal microbial communities. Methods Milk/infant fecal samples from 357 maternal-infant dyads collected as part of the INSPIRE study from 11 geographically/culturally diverse sites located in eight countries (Ethiopia, The Gambia, Ghana, Kenya, Peru, Spain, Sweden, and USA) were analyzed. DNA was extracted and bacterial 16S rRNA V1V3 hypervariable region amplified/sequenced for microbiome analysis. HMO, lactose, and protein profiles were generated from HPLC and spectrophotometric assays. Results Milk and infant feces share many of the same abundant bacterial genera, while also containing unique bacterial communities. Community states type (CST) analyses indicate both sample types group into a relatively small number of discrete communities characterized by enrichment of specific taxa (e.g., Streptococcus, Bifidobacterium). Concentrations of milk lactose and protein varied by population/CST. Additionally, variation in the microbial community structure of milk and infant feces was associated with concentrations of total/individual HMO, lactose, and protein. Conclusions Similar to HMO concentrations, milk lactose and protein vary globally. Variations in milk and infant fecal microbial communities are associated with those of milk lactose, protein, and HMO concentrations. Given these results, as well as prior data on the influence of other environmental variables (e.g., pumped vs. direct breastfeeding), additional longitudinal studies are needed to better understand this complex network of maternal-infant-microbe interactions with respect to environmental factors and how differences impact postnatal maternal-infant health. Funding Sources National Science Foundation (award 1,344,288), National Institutes of Health (R01 HD092297), and USDA.

Intraneural Recordings in Rat Vagus Nerves Using Carbon Fiber Microelectrode Arrays v1

This protocol is for obtaining physiological action potential recordings in rat vagus nerves using carbon fiber microelectrode arrays (CFMAs) in spontaneous and blood glucose and breathing modulated conditions. The rats were anesthetized with isoflurane, which maintained consistent and stable depth of anesthesia for recording vagal nerve activity with ultra-small carbon fibers. Blood glucose levels were modulated by intraperitoneal (IP) injection of glucose, insulin, or 2-deoxy-D-glucose (2-DG). Breathing was modulated by increasing anesthesia depth. Carbon fiber microelectrode arrays are available through the Multimodal Integrated Neural Technologies (MINT) technology hub (https://mint.engin.umich.edu/), which is supported by the National Science Foundation (Award 1707316). This research was also supported by the National Institute of Health SPARC Program (Award OT2OD024907).