A clinical consensus paper on jejunal tube feeding in children.

BACKGROUND: Feeding problems are common in children with complex medical problems or acute critical illness and enteral nutrition may be required. In certain situations, gastric tube feeding is poorly tolerated or may not be feasible. When feed intolerance persists despite appropriate adjustments to oral and gastric enteral regimens, jejunal tube feeding can be considered as an option for nutrition support. METHODS: A multidisciplinary expert working group of the Australasian Society of Parenteral and Enteral Nutrition was convened. They identified topic questions and five key areas of jejunal tube feeding in children. Literatures searches were undertaken on Pubmed, Embase, and Medline for all relevant studies, between January 2000 and September 2022 (n = 103). Studies were assessed using National Health and Medical Research Council guidelines to generate statements, which were discussed as a group, followed by voting on statements using a modified Delphi process to determine consensus. RESULTS: A total of 24 consensus statements were created for five key areas: patient selection, type and selection of feeding tube, complications, clinical use of jejunal tubes, follow-up, and reassessment. CONCLUSION: Jejunal tube feeding is a safe and effective means of providing nutrition in a select group of pediatric patients with complex medical needs, who are unable to be fed by gastric tube feeding. Appropriate patient selection is important as complications associated with jejunal tube feeding are not uncommon, and although mostly minor, can be significant or require tube reinsertion. All children receiving jejunal tube feeding should have multidisciplinary team assessment and follow-up.

BMI1 regulates human erythroid self-renewal through both gene repression and gene activation.

The limited proliferative capacity of erythroid precursors is a major obstacle to generate sufficient numbers of in vitro-derived red blood cells (RBC) for clinical purposes. We and others have determined that BMI1, a member of the polycomb repressive complex 1 (PRC1), is both necessary and sufficient to drive extensive proliferation of self-renewing erythroblasts (SREs). However, the mechanisms of BMI1 action remain poorly understood. BMI1 overexpression led to 10 billion-fold increase BMI1-induced (i)SRE self-renewal. Despite prolonged culture and BMI1 overexpression, human iSREs can terminally mature and agglutinate with typing reagent monoclonal antibodies against conventional RBC antigens. BMI1 and RING1B occupancy, along with repressive histone marks, were identified at known BMI1 target genes, including the INK-ARF locus, consistent with an altered cell cycle following BMI1 inhibition. We also identified upregulated BMI1 target genes with low repressive histone modifications, including key regulator of cholesterol homeostasis. Functional studies suggest that both cholesterol import and synthesis are essential for BMI1-associated self-renewal. These findings support the hypothesis that BMI1 regulates erythroid self-renewal not only through gene repression but also through gene activation and offer a strategy to expand the pool of immature erythroid precursors for eventual clinical uses.

Intractable Feeding Intolerance in Children With Severe Neurological Impairment: A Retrospective Case Review of Nine Children Known to a Pediatric Palliative Care Service.

BACKGROUND: Intractable feeding intolerance in children with severe neurological impairment (SNI) is poorly defined and understood. OBJECTIVES: (1) To describe 9 children with SNI, where intractable feeding intolerance was thought to be a contributor to their deterioration or death. (2) To consider terminology to describe the severe end of the spectrum of feeding difficulties in children with SNI. RESULTS: Mean age at death was 10.3 years (range: 5 - 15.6), and median time from palliative care referral to death was 3.1 months. Location of death was home (n = 3), hospice (n = 1), and hospital (n = 5) with 1 death in intensive care. Gastrointestinal "failure" or "dysfunction" were documented for 7 children, (median time between documentation and death was 3.9 months (range: .1 to 13.1)). All children were fed via a gastrostomy tube during their life (median age of insertion 2.5 years (range: 1.2 to 6.8 years)), and 7 via the jejunal route (median age of insertion 9.2 years (range 2.4 to 14.7 years)). Children lived a median of 9 percent of their lives after jejunal tube feeding was commenced. No child had home-based parenteral nutrition. Multiple symptom management medications were required. CONCLUSION: 'Intractable feeding intolerance' describes a clinical crossroads in a child's life where there is an opportunity to consider the appropriateness of further interventions. Further work should explore predictors of intractable feeding intolerance and the delicate balance between cause or contributor to death. The importance of clinician-family prognostic conversations and goal-concordant care both during life and in the terminal phase is highlighted.

Infusing intellectual and Developmental disability training into Medical School curriculum: a Pilot intervention.

PURPOSE: Despite the rising prevalence of developmental disabilities (DD) in the US, there remains insufficient training for healthcare professionals to care for this medically underserved population - particularly adults. The National Inclusive Curriculum for Health Education (NICHE) aims to improve attitudes and knowledge towards people with intellectual and developmental disabilities (PWIDD); herein we describe one such intervention. METHOD: The intervention integrated didactic, panel presentation and clinical skills components into a 2nd year medical school curriculum.  The didactic session, covering  health and assessment of PWIDDs, history of IDD, stigma, etc., was co-taught by a developmental pediatrician, family medicine physician and social worker.  A panel of 3 adult self-advocates (SAs) with DD and a parent of a child with DD spoke about their lived experiences.  One week later, students practiced taking clinical histories of SAs within small group settings with adult PWIDDs, facilitated by medical school faculty. Students completed the NICHE Knowledge(49 items) and Attitudes (60 items) surveys. The evaluation analyzed pre/post intervention differences in a) knowledge and attitude scores overall and b) by student age, gender, intended medical specialty, and prior experiences with PWIDDs. Open-ended comments were analyzed with content analysis. RESULTS: Overall Knowledge scores increased from pre-to posttest (n = 85; 65[19] vs. 73[17], p = 0.00), while Attitudes score improved (i.e., decreased) (n = 88; 0.55 [.06] vs. 0.53 [0.06]); p = 0.00).  Higher pretest knowledge was found among female identified students (vs. others; p = 0.01) and those knowing > = 5 PWIDD (vs < 5; p = 0.02).  Students characterize their IDD training and experience prior to intervention as 'lacking' and described the sessions as effective. CONCLUSIONS: A brief (4 hours total) intervention was associated with modest but significant improved knowledge and attitudes towards PWIDDs. Replication and sustainability of this and other NICHE interventions are needed to fill gaps in PWIDDs' health care.

Transfusion of Adult, but Not Neonatal, Platelets Promotes Monocyte Trafficking in Neonatal Mice.

BACKGROUND: Thrombocytopenia is common in preterm neonates. Platelet transfusions are sometimes given to thrombocytopenic neonates with the hope of reducing the bleeding risk, however, there are little clinical data to support this practice, and platelet transfusions may increase the bleeding risk or lead to adverse complications. Our group previously reported that fetal platelets expressed lower levels of immune-related mRNA compared with adult platelets. In this study, we focused on the effects of adult versus neonatal platelets on monocyte immune functions that may have an impact on neonatal immune function and transfusion complications. METHODS: Using RNA sequencing of postnatal day 7 and adult platelets, we determined age-dependent platelet gene expression. Platelets and naive bone marrow-isolated monocytes were cocultured and monocyte phenotypes determined by RNA sequencing and flow cytometry. An in vivo model of platelet transfusion in neonatal thrombocytopenic mice was used in which platelet-deficient TPOR (thrombopoietin receptor) mutant mice were transfused with adult or postnatal day 7 platelets and monocyte phenotypes and trafficking were determined. RESULTS: Adult and neonatal platelets had differential immune molecule expression, including Selp. Monocytes incubated with adult or neonatal mouse platelets had similar inflammatory (Ly6Chi) but different trafficking phenotypes, as defined by CCR2 and CCR5 mRNA and surface expression. Blocking P-sel (P-selectin) interactions with its PSGL-1 (P-sel glycoprotein ligand-1) receptor on monocytes limited the adult platelet-induced monocyte trafficking phenotype, as well as adult platelet-induced monocyte migration in vitro. Similar results were seen in vivo, when thrombocytopenic neonatal mice were transfused with adult or postnatal day 7 platelets; adult platelets increased monocyte CCR2 and CCR5, as well as monocyte chemokine migration, whereas postnatal day 7 platelets did not. CONCLUSIONS: These data provide comparative insights into adult and neonatal platelet transfusion-regulated monocyte functions. The transfusion of adult platelets to neonatal mice was associated with an acute inflammatory and trafficking monocyte phenotype that was platelet P-sel dependent and may have an impact on complications associated with neonatal platelet transfusions.

Mammalian life depends on two distinct pathways of DNA damage tolerance.

DNA damage threatens genomic integrity and instigates stem cell failure. To bypass genotoxic lesions during replication, cells employ DNA damage tolerance (DDT), which is regulated via PCNA ubiquitination and REV1. DDT is conserved in all domains of life, yet its relevance in mammals remains unclear. Here, we show that inactivation of both PCNA-ubiquitination and REV1 results in embryonic and adult lethality, and the accumulation of DNA damage in hematopoietic stem and progenitor cells (HSPCs) that ultimately resulted in their depletion. Our results reveal the crucial relevance of DDT in the maintenance of stem cell compartments and mammalian life in unperturbed conditions.

Description of a Dialectical Behavior Therapy program in a Veterans Affairs Health Care System.

A comprehensive Dialectical Behavior Therapy (DBT) program was created within a VA Health Care System for patients with recent psychiatric hospitalization, suicidality and/or significant emotion dysregulation. The program was notable for being one of a relatively small number of comprehensive DBT programs in the VA system, and for including patients with psychosis and psychotic disorder, with a majority of patients (58%) having a documented history of psychosis or endorsing psychotic symptoms in assessments. We describe the process of creating this program at a VA medical center and present preliminary program evaluation data. All patients completed assessments of suicidality (C-SSRS), emotion dysregulation (DERS), skills use and dysfunctional coping (DBT-WCCL), borderline symptomatology (BSL-23), and depression (PHQ-9) at program entry and subsequently every 6-8 weeks through program completion. Suicide attempts and hospitalizations were also tracked. Twelve patients completed multiple (up to six) assessment timepoints, allowing for evaluation of change during treatment. Patients demonstrated improvements on most measures and no hospitalizations or suicide attempts during active treatment, and the subsample with psychosis showed average improvements on every outcome measure. Eleven of 12 patients completed a full six-month rotation.

Exclusive enteral nutrition: An optimal care pathway for use in children with active luminal Crohn's disease.

AIM: Exclusive enteral nutrition (EEN) is recommended as a first-line therapy for active luminal paediatric Crohn's disease, by many contemporary consensus guidelines. However, EEN protocols vary internationally. A key enabler for the use of EEN therapy has been identified as the standardisation of protocols. The aim of this study was to develop an optimal care pathway for use of EEN in children with active luminal Crohn's disease. METHODS: A working group of 11 paediatric gastroenterology dietitians and one paediatric gastroenterologist from Australia and New Zealand was convened to develop a standard optimal care pathway. Seven key areas were identified; clinical indications, workup assessments, EEN prescription, monitoring, food reintroduction, partial enteral nutrition and maintenance enteral nutrition. Recent literature was reviewed, assessed according to the National Health and Medical Research Council guidelines, and consensus statements were developed and voted on. Consensus opinion was used where literature gaps existed. RESULTS: A total of nineteen consensus statements from the seven key areas were agreed upon. The consensus statements informed the optimal care pathway for children with active luminal undertaking EEN in Australia and New Zealand. CONCLUSION: This study developed an EEN optimal care pathway to facilitate standardisation of clinical care for children with active luminal Crohn's disease, and hopefully improve clinical outcomes and identify areas for future research.

Circulating primitive murine erythroblasts undergo complex proteomic and metabolomic changes during terminal maturation.

Primitive erythropoiesis is a critical component of the fetal cardiovascular network and is essential for the growth and survival of the mammalian embryo. The need to rapidly establish a functional cardiovascular system is met, in part, by the intravascular circulation of primitive erythroid precursors that mature as a single semisynchronous cohort. To better understand the processes that regulate erythroid precursor maturation, we analyzed the proteome, metabolome, and lipidome of primitive erythroblasts isolated from embryonic day (E) 10.5 and E12.5 of mouse gestation, representing their transition from basophilic erythroblast to orthochromatic erythroblast (OrthoE) stages of maturation. Previous transcriptional and biomechanical characterizations of these precursors have highlighted a transition toward the expression of protein elements characteristic of mature red blood cell structure and function. Our analysis confirmed a loss of organelle-specific protein components involved in messenger RNA processing, proteostasis, and metabolism. In parallel, we observed metabolic rewiring toward the pentose phosphate pathway, glycolysis, and the Rapoport-Luebering shunt. Activation of the pentose phosphate pathway in particular may have stemmed from increased expression of hemoglobin chains and band 3, which together control oxygen-dependent metabolic modulation. Increased expression of several antioxidant enzymes also indicated modification to redox homeostasis. In addition, accumulation of oxylipins and cholesteryl esters in primitive OrthoE cells was paralleled by increased transcript levels of the p53-regulated cholesterol transporter (ABCA1) and decreased transcript levels of cholesterol synthetic enzymes. The present study characterizes the extensive metabolic rewiring that occurs in primary embryonic erythroid precursors as they prepare to enucleate and continue circulating without internal organelles.

COVID-19 vaccine perceptions in New York State's intellectual and developmental disabilities community.

BACKGROUND: People with intellectual and developmental disabilities (IDD) are at disproportionate risk for severe COVID-19 outcomes, particularly those living in congregate care settings. Yet, there is limited data on vaccine perceptions in the disability community. OBJECTIVE: To explore COVID-19 vaccine perceptions in individuals with IDD, their family members, and those who work with them, to inform a statewide vaccine information and messaging project. METHODS: A national survey, adapted in five languages for the IDD community, was distributed to a convenience sample of IDD organizations throughout New York State. Constructs included vaccine intention, reasons for vaccine hesitancy, and trusted sources of vaccine information. Zip code data were used to map respondent location and vaccine preferences. RESULTS: Of n = 825 respondents, approximately 75% intended to or had received the vaccine across roles (i.e., people with developmental disabilities, family members, direct care workers) and racial/ethnic groups. Greater vaccine hesitancy was reported in younger individuals and those making decisions on behalf of a person with IDD. Concerns included side effects and the swiftness of vaccine development. Black and Hispanic participants had heightened concerns about being an "experiment" for the vaccine. Trusted sources of information included healthcare providers and family members. Respondents who intended to/received the vaccine were dispersed throughout the state. CONCLUSIONS: Vaccine preferences in this New York State disability community sample align with national data. Identified concerns suggest the need for community education that addresses misperceptions. Age and race differences in perspectives highlight the need for tailored education, delivered by trusted messengers.

Modeling human yolk sac hematopoiesis with pluripotent stem cells.

In the mouse, the first hematopoietic cells are generated in the yolk sac from the primitive, erythro-myeloid progenitor (EMP) and lymphoid programs that are specified before the emergence of hematopoietic stem cells. While many of the yolk sac-derived populations are transient, specific immune cell progeny seed developing tissues, where they function into adult life. To access the human equivalent of these lineages, we modeled yolk sac hematopoietic development using pluripotent stem cell differentiation. Here, we show that the combination of Activin A, BMP4, and FGF2 induces a population of KDR+CD235a/b+ mesoderm that gives rise to the spectrum of erythroid, myeloid, and T lymphoid lineages characteristic of the mouse yolk sac hematopoietic programs, including the Vδ2+ subset of γ/δ T cells that develops early in the human embryo. Through clonal analyses, we identified a multipotent hematopoietic progenitor with erythroid, myeloid, and T lymphoid potential, suggesting that the yolk sac EMP and lymphoid lineages may develop from a common progenitor.

Language Disorders Research on Bilingualism, School-Age, and Related Difficulties: A Scoping Review of Descriptive Studies.

BACKGROUND: Developmental language disorder (DLD) often remains undetected until children shift from 'learning to read' to 'reading to learn,' around 9 years of age. Mono- and bilingual children with DLD frequently have co-occurring reading, attention, and related difficulties, compared to children with typical language development (TLD). Data for mono- and bilingual children with DLD and TLD would aid differentiation of language differences versus disorders in bilingual children. OBJECTIVE: We conducted a scoping review of descriptive research on mono-and bilingual children < and >= 9 years old with DLD versus TLD, and related skills (auditory processing, attention, cognition, executive function, and reading). DATA SOURCES: We searched PubMed for the terms "bilingual" and "language disorders" or "impairment" and "child[ren]" from August 1, 1979 through October 1, 2018. CHARTING METHODS: Two abstracters charted all search results. Main exclusions were: secondary data/reviews, special populations, intervention studies, and case studies/series. Abstracted data included age, related skills measures', and four language groups of participants: monolingual DLD, monolingual TLD, bilingual DLD, and bilingual TLD. RESULTS: Of 366 articles, 159 (43%) met inclusion criteria. Relatively few (14%, n = 22) included all 4 language groups, co-occurring difficulties other than nonverbal intelligence (n = 49, 31%) or reading (n = 51, 32%) or any 9-18 year-olds (31%, n = 48). Just 5 (3%) included only 9-18 year-olds. Among studies with any 9 to 18 year olds, just 4 (8%, 4/48) included 4 language groups. CONCLUSIONS: Future research should include mono- and bilingual children with both DLD and TLD, beyond 8 years of age, along with data about their related skills.

Fat soluble vitamin status in children on home parenteral nutrition in a tertiary paediatric intestinal rehabilitation unit.

BACKGROUNDS & AIMS: Children with intestinal failure on home parenteral nutrition are at risk of fat malabsorption and fat soluble vitamin deficiency. Fish oil containing mixed lipid emulsions (SMOFlipid®) with higher vitamin E content, have a theoretical risk of exceeding current recommendations for vitamin E dosing and, may influence other fat soluble vitamin status in these children. The aim of this study was to assess for fat soluble vitamin status in children on long-term home parental nutrition receiving a mixed lipid emulsion (SMOFlipid®) compared with those receiving traditional soy or soy/olive oil based (non- SMOFlipid®) lipid emulsions and whether this is influenced by the underlying cause of intestinal failure. METHODS: Retrospective longitudinal study in a tertiary referral paediatric hospital of children on home parental nutrition during the period January 2000 to June 2019. Data was retrieved using medical and pharmacy records, laboratory database, and summarised using inferential statistics. RESULTS: 111 patients (n = 58 female) received home parental nutrition in 121 discrete episodes (range 45-5329 days). N = 61 (55%) were diagnosed with anatomical short bowel syndrome, of which necrotising enterocolitis was the most common cause (n = 14). SMOFlipid® was used exclusively in n = 79 patients, non-SMOFlipid® exclusively in n = 19, and n = 13 changed from non-SMOFlipid® to SMOFlipid® during the study period. The median vitamin E level and vitamin E:lipid ratio were significantly higher for patients on SMOFlipid® compared to non-SMOFlipid® (27.9 vs 18.3 µmol/L respectively, p < 0.001; 7.10 vs 4.00 µmol/mmol; p < 0.001). Median vitamin A level was comparable (1.19 vs 1.12 µmol/L, p = 0.241), while median vitamin D level was significantly lower in the non-SMOFlipid® group consistent with mild deficiency (63.7 vs 43.0 nmol/L, p < 0.001). CONCLUSION: The use of SMOFlipid® correlated with higher Vitamin E level in paediatric home parental nutrition patients. Lower vitamin D level appears to correlate with the use of non-SMOFlipid®. A larger prospective cohort is required to delineate any clinical significance from these findings.

Mds1CreERT2, an inducible Cre allele specific to adult-repopulating hematopoietic stem cells.

Hematopoietic ontogeny consists of two broad programs: an initial hematopoietic stem cell (HSC)-independent program followed by HSC-dependent hematopoiesis that sequentially seed the fetal liver and generate blood cells. However, the transition from HSC-independent to HSC-derived hematopoiesis remains poorly characterized. To help resolve this question, we developed Mds1CreERT2 mice, which inducibly express Cre-recombinase in emerging HSCs in the aorta and label long-term adult HSCs, but not HSC-independent yolk-sac-derived primitive or definitive erythromyeloid (EMP) hematopoiesis. Our lineage-tracing studies indicate that HSC-derived erythroid, myeloid, and lymphoid progeny significantly expand in the liver and blood stream between E14.5 and E16.5. Additionally, we find that HSCs contribute the majority of F4/80+ macrophages in adult spleen and marrow, in contrast to their limited contribution to macrophage populations in brain, liver, and lungs. The Mds1CreERT2 mouse model will be useful to deconvolute the complexity of hematopoiesis as it unfolds in the embryo and functions postnatally.

ß2M Signals Monocytes Through Non-Canonical TGFß Receptor Signal Transduction.

RATIONALE: Circulating monocytes can have proinflammatory or proreparative phenotypes. The endogenous signaling molecules and pathways that regulate monocyte polarization in vivo are poorly understood. We have shown that platelet-derived ß2M (ß-2 microglobulin) and TGF-ß (transforming growth factor ß) have opposing effects on monocytes by inducing inflammatory and reparative phenotypes, respectively, but each bind and signal through the same receptor. We now define the signaling pathways involved. OBJECTIVE: To determine the molecular mechanisms and signal transduction pathways by which ß2M and TGF-ß regulate monocyte responses both in vitro and in vivo. METHODS AND RESULTS: Wild-type- (WT) and platelet-specific ß2M knockout mice were treated intravenously with either ß2M or TGF-ß to increase plasma concentrations to those in cardiovascular diseases. Elevated plasma ß2M increased proinflammatory monocytes, while increased plasma TGFß increased proreparative monocytes. TGF-ßR (TGF-ß receptor) inhibition blunted monocyte responses to both ß2M and TGF-ß in vivo. Using imaging flow cytometry, we found that ß2M decreased monocyte SMAD2/3 nuclear localization, while TGF-ß promoted SMAD nuclear translocation but decreased noncanonical/inflammatory (JNK [jun kinase] and NF-κB [nuclear factor-κB] nuclear localization). This was confirmed in vitro using both imaging flow cytometry and immunoblots. ß2M, but not TGF-ß, promoted ubiquitination of SMAD3 and SMAD4, that inhibited their nuclear trafficking. Inhibition of ubiquitin ligase activity blocked noncanonical SMAD-independent monocyte signaling and skewed monocytes towards a proreparative monocyte response. CONCLUSIONS: Our findings indicate that elevated plasma ß2M and TGF-ß dichotomously polarize monocytes. Furthermore, these immune molecules share a common receptor but induce SMAD-dependent canonical signaling (TGF-ß) versus noncanonical SMAD-independent signaling (ß2M) in a ubiquitin ligase dependent manner. This work has broad implications as ß2M is increased in several inflammatory conditions, while TGF-ß is increased in fibrotic diseases. Graphic Abstract: A graphic abstract is available for this article.

Sleep problem screening of young children by speech-language pathologists: A mixed-methods feasibility study.

Background & Aims: Poor sleep in young children imperils language learning and use. Both sleep and language problems are prevalent in early childhood. Speech-language pathologists are in a unique position to expand surveillance of sleep problems, which in turn may contribute to communication difficulties. We conducted a feasibility study of speech-language pathologist screening for behavioral sleep problems and sleep-disordered breathing symptoms at a multidisciplinary evaluation and treatment center. Methods: Speech-language pathologists administered screeners to parents of 2-6-year-olds: the Short Form-Children's Sleep Habits Questionnaire (for behavioral sleep problems) which includes an item asking if the child has a sleep problem (yes/no), and the pediatric sleep questionnaire (for sleep-disordered breathing). Speech-language pathologists participated in pre- and post-screening focus groups. Pre-screening topics included professional preparation and clinical experience regarding pediatric sleep issues. Post-screening, speech-language pathologists provided feedback about the screening experience and feasibility of incorporating such screening into practice. Results: Among 51 children, 31% (16/51) screened positive for sleep-disordered breathing, 78% for behavioral sleep problems (40/51), and 43% (12/28) per parent report. Parent-reported problems were associated with sleep-disordered breathing (p = 0.00) but not behavioral sleep problems (p = 0.24). During focus groups, speech-language pathologists reported no formal pediatric sleep training, high parent concern about sleep, and agreed that screening fit their professional mandate. Speech-language pathologists affirmed that the ≤15 min screenings integrated seamlessly into practice but that additional training, particularly for sleep-disordered breathing, was needed. Conclusions: The prevalence of sleep problems in 2-6-year-olds presenting to speech-language pathologists was higher than in community samples, but consistent with data from young children with developmental disabilities. Speech-language pathologists endorsed the utility and feasibility of sleep problem screening and education in their clinical practice. Implications: Integrating sleep problem screening and education into speech-language pathologist practice is feasible and could widen surveillance of both sleep problems and risk factors for developmental language disorders. Further research should include larger samples and other settings, e.g. home or school.

Lung megakaryocytes are immune modulatory cells.

Although platelets are the cellular mediators of thrombosis, they are also immune cells. Platelets interact both directly and indirectly with immune cells, impacting their activation and differentiation, as well as all phases of the immune response. Megakaryocytes (Mks) are the cell source of circulating platelets, and until recently Mks were typically only considered bone marrow-resident (BM-resident) cells. However, platelet-producing Mks also reside in the lung, and lung Mks express greater levels of immune molecules compared with BM Mks. We therefore sought to define the immune functions of lung Mks. Using single-cell RNA sequencing of BM and lung myeloid-enriched cells, we found that lung Mks, which we term MkL, had gene expression patterns that are similar to antigen-presenting cells. This was confirmed using imaging and conventional flow cytometry. The immune phenotype of Mks was plastic and driven by the tissue immune environment, as evidenced by BM Mks having an MkL-like phenotype under the influence of pathogen receptor challenge and lung-associated immune molecules, such as IL-33. Our in vitro and in vivo assays demonstrated that MkL internalized and processed both antigenic proteins and bacterial pathogens. Furthermore, MkL induced CD4+ T cell activation in an MHC II-dependent manner both in vitro and in vivo. These data indicated that MkL had key immune regulatory roles dictated in part by the tissue environment.

Pulmonary Manifestations of Gastrointestinal, Pancreatic, and Liver Diseases in Children.

Pulmonary manifestations of gastrointestinal (GI) diseases are often subtle, and underlying disease may precede overt symptoms. A high index of suspicion and a low threshold for consultation with a pediatric pulmonologist is warranted in common GI conditions. This article outlines the pulmonary manifestations of different GI, pancreatic, and liver diseases in children, including gastroesophageal reflux disease, inflammatory bowel disease, pancreatitis, alpha1-antitrypsin deficiency, nonalcoholic fatty liver disease, and complications of chronic liver disease (hepatopulmonary syndrome and portopulmonary hypertension).