27 research outputs found
Case 28-2019: A 22-Year-Old Woman with Dyspnea and Chest Pain
Case report on a 22-year-old woman who was seen in the pediatric pulmonary clinic of this hospital because of chest pain, cough, and dyspnea on exertion
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Development of a Primary Human Co-Culture Model of Inflamed Airway Mucosa
Neutrophil breach of the mucosal surface is a common pathological consequence of infection. We present an advanced co-culture model to explore neutrophil transepithelial migration utilizing airway mucosal barriers differentiated from primary human airway basal cells and examined by advanced imaging. Human airway basal cells were differentiated and cultured at air-liquid interface (ALI) on the underside of 3 µm pore-sized transwells, compatible with the study of transmigrating neutrophils. Inverted ALIs exhibit beating cilia and mucus production, consistent with conventional ALIs, as visualized by micro-optical coherence tomography (µOCT). µOCT is a recently developed imaging modality with the capacity for real time two- and three-dimensional analysis of cellular events in marked detail, including neutrophil transmigratory dynamics. Further, the newly devised and imaged primary co-culture model recapitulates key molecular mechanisms that underlie bacteria-induced neutrophil transepithelial migration previously characterized using cell line-based models. Neutrophils respond to imposed chemotactic gradients, and migrate in response to Pseudomonas aeruginosa infection of primary ALI barriers through a hepoxilin A3-directed mechanism. This primary cell-based co-culture system combined with µOCT imaging offers significant opportunity to probe, in great detail, micro-anatomical and mechanistic features of bacteria-induced neutrophil transepithelial migration and other important immunological and physiological processes at the mucosal surface
Genetic Causes of Interstitial Lung Disease in Children
Abstract Interstitial lung diseases (ILDs) occur through out childhood and adult life. In neonates and infants, defects in lung development and growth and defects in surfactant production and function are common features with the environmental factors being less important. For older children, genetic background combined with environmental exposure is central to the pathophysiology of ILD. In adults, environmental exposure becomes more critical to mechanism of disease with genetic background becoming less essential. Thus ILDs are often multifactorial in origin but recently molecular genetic defects have been described, especially in children. Thus, genetic testing is a non-invasive investigation that is likely to identify the genetic underpinning of childhood interstitial lung diseases (chILD). This is likely to provide insights into the mechanism of disease, which that may be helpful for treatment and defining the prognosis. This review summarizes genetic defects that can lead to ILDs, and highlights the recent advances in several kinds of chILD
Pneumocystis Activates Human Alveolar Macrophage NF-κB Signaling through Mannose Receptors
Alveolar macrophages (AM) represent important effector cells in the innate immune response to the AIDS-related pathogen Pneumocystis, but the early AM host defense signaling events are poorly defined. Using AM from healthy individuals, we showed in the present study that Pneumocystis organisms stimulate AM NF-κB p50 and p65 nuclear translocation in a time-dependent and multiplicity-of-infection-dependent manner as determined by electrophoretic mobility shift assay and immunofluorescence microscopy and that NF-κB nuclear translocation is associated with I-κB phosphorylation. Importantly, competitive inhibition of mannose receptor and targeted short interfering RNA-mediated gene suppression of mannose receptor mRNA and protein is associated with complete elimination of NF-κB nuclear translocation in response to Pneumocystis. Furthermore, human immunodeficiency virus (HIV) infection of AM (as a model human disease state of reduced AM mannose receptor expression and function) inhibits Pneumocystis-mediated NF-κB nuclear translocation and is associated with reduced I-κB phosphorylation and reduced interleukin-8 (IL-8) release. In contrast, NF-κB nuclear translocation and IL-8 release in response to lipopolysaccharide are intact in AM from both healthy and HIV-infected individuals, indicating that the observed impairment is not a global disturbance of the NF-κB pathway. Thus, in addition to phagocytic and endocytic effector functions, the present study identifies mannose receptors as pattern recognition receptors capable of NF-κB activation in response to infectious non-self challenge. AM mannose receptor-mediated NF-κB activation may represent an important mechanism of the host cell response to Pneumocystis, and altered NF-κB activation in the context of HIV infection may impair a critical innate immune signaling response and may contribute to pathogenesis of opportunistic lung infections
"Friending" teens: systematic review of social media in adolescent and young adult health care.
BACKGROUND: Social media has emerged as a potentially powerful medium for communication with adolescents and young adults around their health choices.
OBJECTIVE: The goal of this systematic review is to identify research on the use of social media for interacting with adolescents and young adults in order to achieve positive health outcomes.
METHODS: A MEDLINE/PubMed electronic database search was performed between January 1, 2002 and October 1, 2013, using terms to identify peer-reviewed research in which social media and other Web 2.0 technologies were an important feature. We used a systematic approach to retrieve papers and extract relevant data.
RESULTS: We identified 288 studies involving social media, of which 87 met criteria for inclusion; 75 studies were purely observational and 12 were interventional. The ways in which social media was leveraged by these studies included (1) observing adolescent and young adult behavior (n=77), (2) providing health information (n=13), (3) engaging the adolescent and young adult community (n=17), and (4) recruiting research participants (n=23). Common health topics addressed included high-risk sexual behaviors (n=23), alcohol, tobacco, and other drug use (n=19), Internet safety (n=8), mental health issues (n=18), medical conditions (n=11), or other specified issues (n=12). Several studies used more than one social media platform and addressed more than one health-related topic.
CONCLUSIONS: Social media technologies offer an exciting new means for engaging and communicating with adolescents and young adults; it has been successfully used to engage this age group, identify behaviors, and provide appropriate intervention and education. Nevertheless, the majority of studies to date have been preliminary and limited in their methodologies, and mostly center around evaluating how adolescents and young adults use social media and the resulting implications on their health. Although these explorations are essential, further exploration and development of these strategies into building effective interventions is necessary
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Long-Term Pulmonary Function in Duchenne Muscular Dystrophy: Comparison of Eteplirsen-Treated Patients to Natural History
Background: Duchenne muscular dystrophy (DMD) is a rare, degenerative, X-linked genetic disease that results in progressive muscle loss and premature death, most commonly from respiratory or cardiac failure. DMD is primarily caused by whole exon deletions, resulting in a shift of the dystrophin mRNA reading frame that prevents production of functional dystrophin protein. Eteplirsen, a phosphorodiamidate morpholino oligomer (PMO), is designed to skip exon 51, restore the reading frame, and induce production of internally shortened dystrophin in patients with mutations amenable to such treatment. Objective: Describe lung function assessed throughout eteplirsen studies 201/202. Methods: Studies 201/202 included 12 patients treated with eteplirsen over 5 years. Pulmonary function tests included forced vital capacity (FVC), maximum expiratory pressure (MEP), and maximum inspiratory pressure (MIP). With no long-term placebo control, FVC results were compared with data from the United Dystrophinopathy Project (UDP). MIP and MEP were compared to published natural history. Results: Age-adjusted mixed-model repeated-measures analysis showed decreases of 2.3% and 2.6% annually for FVC% p and MEP% p, and an annual increase of 0.6% for MIP% p for the eteplirsen-treated cohort. Data from the UDP demonstrated a 4.1% decline in FVC% p. The published natural history reports annual declines of at least 2.7% and 3.8% for MEP% p and MIP% p, respectively, in patients with DMD. Conclusions: With eteplirsen treatment, deterioration of respiratory muscle function based on FVC% p was half of that seen in the UDP; MEP% p and MIP% p compared favorably with natural history
Decreased mitogen activated protein kinase activities in congenital diaphragmatic hernia-associated pulmonary hypoplasia
Background/purpose: The mechanisms that cause pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) currently are unknown. The authors proposed that the reduced size and immaturity of these lungs may be associated with differences in the levels of mitogen activated protein (MAP) kinase phosphorylation (extracellular signal regulated protein kinases, ERK-1 and -2).Methods: ERK-1 activities were measured using immune-complex kinase assays on fetal whole-lung lysates obtained from both nitrofen and olive oil-treated (control) pregnant rats. In addition, ERK-1 and ERK-2 functional activities were estimated by semiquantitative Western blot analysis, using an antibody specific for the diphosphorylated (dp-ERK, activated) forms of the enzymes.Results: ERK-1 activities, measured using immune-complex kinase assays, were reduced in CDH lungs compared with olive oil-treated controls (P \u3c.02). In addition, dp-ERK-1 and dp-ERK-2 levels were found to be reduced in CDH lungs compared with controls (dp-ERK-1, P =.003; dp-ERK-2, P =.04), whereas ERK-1 and ERK-2 protein levels were unchanged.Conclusions: The lower values of ERK-1 activity and reduced amounts of dp-ERK-1 and dp-ERK-2 in lung tissue from CDH animals, suggests that ERK-1 and ERK-2 activities are reduced in pulmonary hypoplasia associated with CDH. The observed reduction in ERK-1 and ERK-2 activities implicates attenuated cell signaling upstream of the ERK-1 and -2 enzymes