Maternal Attitudes and Other Factors Associated with Infant Vaccination Status in the United States, 2011-2014.

OBJECTIVE: To assess the role of maternal attitudes and other factors associated with infant vaccination status. STUDY DESIGN: Data on reported vaccination status were analyzed from a nationally representative prospective survey of mothers of 2- to 6-month-old infants. Weighted univariate and multiple logistic regression analyses were conducted. Latent profile analysis of mothers reporting nonimmunized infants identified distinct groups, RESULTS: Of 3268 mothers, 2820 (weighted 86.2%), 311 (9.1%), and 137 (4.7%), respectively, reported their infant had received all, some, or no recommended vaccinations for age. Younger infants and infants with younger mothers were more likely to have received no vaccinations. Mothers with neutral and negative attitudes toward vaccination were >3 (aOR 3.66, 95% CI 1.80-7.46) and 43 times (aOR 43.23, 95% CI 20.28-92.16), respectively, more likely than mothers with positive attitudes to report their infants had received no vaccinations. Two subgroups of mothers reporting that their infants had received no vaccinations were identified: group A (52.5%) had less than positive attitudes and less than positive subjective norms about vaccination (ie, perceived social pressure from others); group B (47.5%) had positive attitudes and positive subjective norms. Group A mothers were more likely to be white (76.1% vs 48.3%, P?=?.002), more educated (43.5% vs 35.4% college or higher, P?=?.02), and to exclusively breastfeed (74.9% vs. 27.3%, P?

Establishment of a Modular Anaerobic Human Intestine Chip.

It is impossible to analyze human-specific host-microbiome interactions using animal models and existing in vitro methods fail to support survival of human cells in direct contact with complex living microbiota for extended times. Here we describe a protocol for culturing human organ-on-a-chip (Organ Chip) microfluidic devices lined by human patient-derived primary intestinal epithelium in the presence of a physiologically relevant transluminal hypoxia gradient that enables their coculture with hundreds of different living aerobic and anaerobic bacteria found within the human gut microbiome. This protocol can be adapted to provide different levels of oxygen tension to facilitate coculturing of microbiome from different regions of gastrointestinal tract, and the same system can be applied with any other type of Organ Chip. This method can help to provide further insight into the host-microbiome interactions that contribute to human health and disease, enable discovery of new microbiome-related diagnostics and therapeutics, and provide a novel approach to advanced personalized medicine.

Plugging the Leaky Pipeline: The Role of Peer Mentorship for Increasing Diversity.

I arrived to my shift early, nervous about caring for critically ill patients as a first-year fellow. I sat in the workroom alone, paralyzed, not sure how to preround despite being months into fellowship. The senior fellow appeared minutes before sign-out; fresh, knowledgeable, and calm, despite her busy night and lack of sleep. She asked me how I was doing. With tears in my eyes, my emotions poured out. I explained that I felt lost, unsure of myself, my place, and my knowledge. For the first time, I confessed out loud, "I don't think I'm supposed to be here. I have no idea what I'm doing." I could trust her in a way I couldn't trust others. She was like me: othered by her identity, minoritized by society. Though different from my own, her identity allowed her to understand my own experiences. We were different from one another and we were also the same. Unlike the senior faculty, it was safe to talk to her. And, unlike my other cofellows, there was a kinship between us in our otherness. She looked at me, closed the door, and shared words of strength that I needed to hear. I belonged. I was more than enough. She shared that the pressure I was experiencing was common among systematically minoritized individuals; she too had felt it before. Sitting with her, I was finally seen, supported, and comforted. As a peer mentor from a minoritized background, she provided a sense of security and belonging that had not been provided in my training and was distinct from the support of senior faculty.

Modeling mucus physiology and pathophysiology in human organs-on-chips.

The surfaces of human internal organs are lined by a mucus layer that ensures symbiotic relationships with commensal microbiome while protecting against potentially injurious environmental chemicals, toxins, and pathogens, and disruption of this layer can contribute to disease development. Studying mucus biology has been challenging due to the lack of physiologically relevant human in vitro models. Here we review recent progress that has been made in the development of human organ-on-a-chip microfluidic culture models that reconstitute epithelial tissue barriers and physiologically relevant mucus layers with a focus on lung, colon, small intestine, cervix and vagina. These organ-on-a-chip models that incorporate dynamic fluid flow, air-liquid interfaces, and physiologically relevant mechanical cues can be used to study mucus composition, mechanics, and structure, as well as investigate its contributions to human health and disease with a level of biomimicry not possible in the past.

Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction.

Environmental enteric dysfunction (EED)-a chronic inflammatory condition of the intestine-is characterized by villus blunting, compromised intestinal barrier function and reduced nutrient absorption. Here we show that essential genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip lined by organoid-derived intestinal epithelial cells from patients with EED and cultured in nutrient-deficient medium lacking niacinamide and tryptophan. Exposure of the organ chip to such nutritional deficiencies resulted in congruent changes in six of the top ten upregulated genes that were comparable to changes seen in samples from patients with EED. Chips lined with healthy epithelium or with EED epithelium exposed to nutritional deficiencies resulted in severe villus blunting and barrier dysfunction, and in the impairment of fatty acid uptake and amino acid transport; and the chips with EED epithelium exhibited heightened secretion of inflammatory cytokines. The organ-chip model of EED-associated intestinal injury may facilitate the analysis of the molecular, genetic and nutritional bases of the disease and the testing of candidate therapeutics for it.

Enteric Coronavirus Infection and Treatment Modeled With an Immunocompetent Human Intestine-On-A-Chip.

Many patients infected with coronaviruses, such as SARS-CoV-2 and NL63 that use ACE2 receptors to infect cells, exhibit gastrointestinal symptoms and viral proteins are found in the human gastrointestinal tract, yet little is known about the inflammatory and pathological effects of coronavirus infection on the human intestine. Here, we used a human intestine-on-a-chip (Intestine Chip) microfluidic culture device lined by patient organoid-derived intestinal epithelium interfaced with human vascular endothelium to study host cellular and inflammatory responses to infection with NL63 coronavirus. These organoid-derived intestinal epithelial cells dramatically increased their ACE2 protein levels when cultured under flow in the presence of peristalsis-like mechanical deformations in the Intestine Chips compared to when cultured statically as organoids or in Transwell inserts. Infection of the intestinal epithelium with NL63 on-chip led to inflammation of the endothelium as demonstrated by loss of barrier function, increased cytokine production, and recruitment of circulating peripheral blood mononuclear cells (PBMCs). Treatment of NL63 infected chips with the approved protease inhibitor drug, nafamostat, inhibited viral entry and resulted in a reduction in both viral load and cytokine secretion, whereas remdesivir, one of the few drugs approved for COVID19 patients, was not found to be effective and it also was toxic to the endothelium. This model of intestinal infection was also used to test the effects of other drugs that have been proposed for potential repurposing against SARS-CoV-2. Taken together, these data suggest that the human Intestine Chip might be useful as a human preclinical model for studying coronavirus related pathology as well as for testing of potential anti-viral or anti-inflammatory therapeutics.

Human Colon-on-a-Chip Enables Continuous In Vitro Analysis of Colon Mucus Layer Accumulation and Physiology.

BACKGROUND & AIMS: The mucus layer in the human colon protects against commensal bacteria and pathogens, and defects in its unique bilayered structure contribute to intestinal disorders, such as ulcerative colitis. However, our understanding of colon physiology is limited by the lack of in vitro models that replicate human colonic mucus layer structure and function. Here, we investigated if combining organ-on-a-chip and organoid technologies can be leveraged to develop a human-relevant in vitro model of colon mucus physiology. METHODS: A human colon-on-a-chip (Colon Chip) microfluidic device lined by primary patient-derived colonic epithelial cells was used to recapitulate mucus bilayer formation, and to visualize mucus accumulation in living cultures noninvasively. RESULTS: The Colon Chip supports spontaneous goblet cell differentiation and accumulation of a mucus bilayer with impenetrable and penetrable layers, and a thickness similar to that observed in the human colon, while maintaining a subpopulation of proliferative epithelial cells. Live imaging of the mucus layer formation on-chip showed that stimulation of the colonic epithelium with prostaglandin E2, which is increased during inflammation, causes rapid mucus volume expansion via an Na-K-Cl cotransporter 1 ion channel-dependent increase in its hydration state, but no increase in de novo mucus secretion. CONCLUSIONS: This study shows the production of colonic mucus with a physiologically relevant bilayer structure in vitro, which can be analyzed in real time noninvasively. The Colon Chip may offer a new preclinical tool to analyze the role of mucus in human intestinal homeostasis as well as diseases, such as ulcerative colitis and cancer.

A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip.

The diverse bacterial populations that comprise the commensal microbiome of the human intestine play a central role in health and disease. A method that sustains complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro would thus enable the investigation of host-microbiome interactions. Here, we show the extended coculture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota, using a microfluidic intestine-on-a-chip that permits the control and real-time assessment of physiologically relevant oxygen gradients. When compared to aerobic coculture conditions, the establishment of a transluminal hypoxia gradient in the chip increased intestinal barrier function and sustained a physiologically relevant level of microbial diversity, consisting of over 200 unique operational taxonomic units from 11 different genera and an abundance of obligate anaerobic bacteria, with ratios of Firmicutes and Bacteroidetes similar to those observed in human faeces. The intestine-on-a-chip may serve as a discovery tool for the development of microbiome-related therapeutics, probiotics and nutraceuticals.

Author Correction: A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip.

In the version of this Article originally published, the authors mistakenly cited Fig. 5d in the sentence beginning 'Importantly, the microbiome cultured in these primary Intestine Chips...'; the correct citation is Supplementary Table 2. This has now been amended.