Innate IFN-lambda responses to dsRNA in the human infant airway epithelium and clinical regulatory factors during viral respiratory infections in early life.

INTRODUCTION: IFN lambda (type III-IFN-λ1) is a molecule primarily produced by epithelial cells that provides an important first-line defence against viral respiratory infections and has been linked to the pathogenesis of viral-induced wheezing in early life. The goal of this study was to better understand the regulation of innate IFN-lambda responses in vitro in primary human infant airway epithelial cells (AECs) and in vivo using nasal aspirates during viral respiratory infections. METHODS: IFN-lambda protein levels were quantified: (a) in human infant AECs exposed to (poly(I:C) dsRNA) under different experimental conditions (n = 8 donors); and (b) in nasal aspirates of young children (≤3 years) hospitalized with viral respiratory infection (n = 138) and in uninfected controls (n = 74). In vivo IFN-lambda airway levels during viral infections were correlated with individual characteristics and respiratory disease parameters. RESULTS: Our in vitro experiments showed that the poly(I:C)-induced innate production of IFN lambda in human infant AECs is regulated by (a) p38-MAPK/NF-kB dependent mechanism; and (b) exposure to pro-inflammatory signals such as IL1ß. Our in vivo studies demonstrated that (a) infants (<18 months) had higher virus-induced IFN-lambda airway secretion; (b) subjects with RSV infection showed the highest IFN-lambda airway levels; and (c) individuals with the highest virus-induced IFN-lambda levels (>90th percentile) had higher viral loads and were more likely to have respiratory sick visits within 12 months of discharge (OR = 5.8). CONCLUSION: IFN-lambda responses to dsRNA in the human infant airway epithelium are regulated by p38-MAPK and NF-kB signalling. High in vivo IFN-lambda production is influenced by virus type and associated with recurrent respiratory sick visits in young children.

Evidence of indirect symbiont conferred protection against the predatory lady beetle Harmonia axyridis in the pea aphid.

BACKGROUND: Defensive symbionts can provide significant fitness advantages to their hosts. Facultative symbionts can protect several species of aphid from fungal pathogens, heat shock, and parasitism by parasitoid wasps. Previous work found that two of these facultative symbionts can also indirectly protect pea aphids from predation by the lady beetle Hippocampus convergens. When aphids reproduce asexually, there is extremely high relatedness among aphid clone-mates and often very limited dispersal. Under these conditions, symbionts may indirectly protect aphid clone-mates from predation by negatively affecting the survival of a predator after the consumption of aphids harboring the same vertically transmitted facultative symbionts. In this study, we wanted to determine whether this indirect protection extended to another lady beetle species, Harmonia axyridis. RESULTS: We fed Ha. axyridis larvae aphids from one of four aphid sub-clonal symbiont lines which all originated from the same naturally symbiont free clonal aphid lineage. Three of the sub-clonal lines harbor different facultative symbionts that were introduced to the lines via microinjection. Therefore these sub-clonal lineages vary primarily in their symbiont composition, not their genetic background. We found that aphid facultative symbionts affected larval survival as well as pupal survival in their predator Ha. axyridis. Additionally, Ha. axyridis larvae fed aphids with the Regiella symbiont had significantly longer larval developmental times than beetle larvae fed other aphids, and females fed aphids with the Regiella symbiont as larvae weighed less as adults. These fitness effects were different from those previously found in another aphid predator Hi. convergens suggesting that the fitness effects may not be the same in different aphid predators. CONCLUSIONS: Overall, our findings suggest that some aphid symbionts may indirectly benefit their clonal aphid hosts by negatively impacting the development and survival of a lady beetle aphid predator Ha. axyridis. By directly affecting the survival of predatory lady beetles, aphid facultative symbionts may increase the survival of their clone-mates that are clustered nearby and have significant impacts across multiple trophic levels. We have now found evidence for multiple aphid facultative symbionts negatively impacting the survival of a second species of aphid predatory lady beetle. These same symbionts also protect their hosts from parasitism and fungal infections, though these fitness effects seem to depend on the aphid species, predator or parasitoid species, and symbiont type. This work further demonstrates that beneficial mutualisms depend upon complex interactions between a variety of players and should be studied in multiple ecologically relevant contexts.

Association Between Congenital Heart Disease-Related Diagnosis Codes and Trauma Surgery Outcomes.

BACKGROUND: Congenital heart disease (CHD) is one the most common congenital anomalies, with a prevalence of 8-10 cases per 1000 live births in the United States. Congenital heart disease has been recognized as a risk factor for poor perioperative and postoperative outcomes in non-cardiac surgery. We aimed to determine if documentation of CHD-related diagnosis codes was associated with similar risks for trauma surgery. METHODS: Data were acquired from the 2010-2019 American College of Surgeons' Trauma Quality Programs Participant Use Files. This study included trauma patients of all ages with one or more surgical procedures and at least one documented non-trauma (comorbidity) International Classification of Diseases code. Patients were stratified based on presence of CHD-related comorbidity codes vs any other comorbidity. Outcomes included mortality, hospital length of stay (LOS), discharge disposition, and in-hospital complications. RESULTS: Using 1:1 propensity score matching, we matched 215 cases with CHD-related comorbid diagnoses to non-CHD controls. Compared to patients with other comorbidities, patients with CHD-related comorbidites were less likely to be discharged home to self-care (odds ratio: 0.44, 95% confidence interval [CI]: 0.25, 078 P = .005) and tended to have prolonged hospital LOS (incidence rate ratio [IRR]: 1.06, 95% CI: 1.001, 1.13, P = .046). CONCLUSIONS: We present the first quantitative multicenter analysis correlating documentation of comorbid CHD-related diagnoses with higher risk of adverse outcomes after trauma surgery. These results support the need to routinely acknowledge and document CHD as comorbidity in trauma admissions that could lead to surgical intervention and for trauma centers to prepare for patients with a possible CHD comorbidity.

Cardiac Surgery Outcomes: A Case for Increased Screening and Treatment of Obstructive Sleep Apnea.

BACKGROUND: Because of the limited published information on complications that obstructive sleep apnea (OSA) patients experience during and after cardiac surgery, we investigated OSA as a risk factor for postoperative outcomes. METHODS: This project used the Northern New England Cardiovascular Disease Study Group's data collected between 2011 and 2017 based on The Society of Thoracic Surgeons Adult Cardiac Surgery Database Data Collections form. A retrospective analysis of 1555 patients with OSA and 10,450 patients without OSA across 5 medical centers undergoing isolated coronary artery bypass grafting, isolated valve surgery, and combined coronary artery bypass grafting valve surgery was conducted. We used 1:1 nearest-neighbor propensity score matching with no replacement to balance characteristics among patients with and without OSA. RESULTS: There was a statistically significant increased risk of postoperative pneumonia, increased length of total and postoperative stay, and time to initial extubation. Two outcomes trended toward significance: intra- and postoperative intraaortic balloon pump use. Outcomes that failed to show statistical significance were surgical site infection, atrial fibrillation, cerebrovascular accident, permanent pacemaker placement, and blood products given. A chart review conducted on a subset of the study cohort revealed that more than 40% of OSA patients did not receive continuous positive airway pressure or bilevel positive airway pressure therapy postoperatively during their hospitalization. CONCLUSIONS: Our study aligns with the literature in concluding that OSA has deleterious effects on postoperative outcomes of cardiac surgery patients. Further research to better stratify OSA patients by severity are still needed. Additionally heightened awareness of the need to screen, diagnose, and properly treat patients for OSA is needed.

Human primary middle ear epithelial cell culture: A novel in vitro model to study otitis media.

OBJECTIVES: Otitis media (OM) is a ubiquitous pediatric disease leading to a significant health care burden. There is no medication beneficial to resolving COM fluid, highlighting the need for research in the field. Crucially, current human middle ear epithelial cell models are transformed cells not recapitulating physiological functions. Herein, we describe a new method to proliferate and differentiate pediatric primary middle ear epithelial cells (pMEEC) from patients as a physiological model for the study of OM. METHODS: We adapted a cell reprogramming protocol using irradiated fibroblast feeder medium in addition to Rho kinase inhibitor to proliferate pMEEC collected during cochlear implant surgery. Cells were plated on transwell membranes, proliferated with conditionally reprogrammed culture medium, and transferred to air-liquid interface (ALI). Cultures were maintained for 4 weeks at ALI, photos were taken and cell lysates and secretions were collected over time for characterization analysis using quantitative polymerase chain reaction, Western bolt, and proteomics. Keratins, MUC5B and MUC5AC mucins, and beta tubulin (TUBB) were analyzed at the mRNA and protein level. RESULTS: Cultures took a mean of 2 weeks to proliferate before transwell plating and forming a tight epithelium at ALI from 2 to 4 weeks. Although mRNA expression of MUC5B, MUC5AC, TUBB, and keratin 5 (KRT5) were variable depending on the differentiation stage and the patient, both TUBB and KRT5 proteins were detected until week 2. CONCLUSION: We demonstrate a novel method to proliferate and differentiate pMEECs that express epithelial markers and that are able to secrete mucins for the study of OM. LEVEL OF EVIDENCE: NA.

Children's Environmental Health in the Digital Era: Understanding Early Screen Exposure as a Preventable Risk Factor for Obesity and Sleep Disorders.

The quantity, accessibility and focus on child-targeted programming has exponentially increased since it entered American households in the early 1900s. It may have started with the television (TV), but technology has evolved and now fits in our pockets; as of 2017, 95% of American families own a smartphone. Availability and child-tailored content has subsequently led to a decrease in the age at initial screen exposure. The negative effects that accompany the current culture of early screen exposure are extensive and need to be considered as technology continues to enter the home and inundate social interactions. Increased levels of early screen exposure have been associated with decreased cognitive abilities, decreased growth, addictive behavior, poor school performance, poor sleep patterns, and increased levels of obesity. Research on the adverse effects of early screen exposure is mounting, but further epidemiological studies are still needed to inform prevention and regulation policies.

Aphid secondary symbionts do not affect prey attractiveness to two species of predatory lady beetles.

Heritable symbionts have been found to mediate interactions between host species and their natural enemies in a variety of organisms. Aphids, their facultative symbionts, and their potential fitness effects have been particularly well-studied. For example, the aphid facultative symbiont Regiella can protect its host from infection from a fungal pathogen, and aphids with Hamiltonella are less likely to be parasitized by parasitic wasps. Recent work has also found there to be negative fitness effects for the larvae of two species of aphidophagous lady beetles that consumed aphids with facultative symbionts. In both species, larvae that consumed aphids with secondary symbionts were significantly less likely to survive to adulthood. In this study we tested whether adult Harmonia axyridis and Hippodamia convergens lady beetles avoided aphids with symbionts in a series of choice experiments. Adults of both lady beetle species were as likely to choose aphids with symbionts as those without, despite the potential negative fitness effects associated with consuming aphids with facultative symbionts. This may suggest that under natural conditions aphid secondary symbionts are not a significant source of selection for predatory lady beetles.