Pediatric negative pressure pulmonary edema: Case series and review of the literature.

INTRODUCTION: Negative pressure pulmonary edema (NPPE) is a potentially life-threatening complication that develops rapidly following acute upper airway obstruction. The condition is rare, dramatic but resolves quickly. Prompt recognition and appropriate supportive treatment may prevent unnecessary investigations and iatrogenic complications. METHODS: We describe a spectrum of etiologies and clinical manifestation of pediatric NPPE in our center and review of previous publications. CONCLUSION: The etiology for the development of NPPE in children has shifted over the years. Although dramatic in presentation, this type of pulmonary edema often resolves quickly with minimal support.

The effect of nose clip on exercise-induced bronchoconstriction in adolescents.

BACKGROUND: Oral breathing is considered to increase hyper-responsiveness of the airways. Data on the need for nose clip (NC) during exercise challenge test (ECT) in children and adolescents is scarce. Ouraim was to evaluate the role of NC during ECT in children and adolescents. METHODS: A prospective, cohort study; children referred for ECT were evaluated on two separate visits, with and without a NC. Demographic, clinical data and measurements of lung functions were recorded. Allergy and asthma control were evaluated by Total Nasal Symptoms Score (TNSS) and Asthma Control Test (ACT) questionnaires. RESULTS: Sixty children and adolescents (mean age 16.7 ± 1.1 years, 38% Female,) performed ECT with NC and 48 (80%) completed visit 2 (ECT without NC), 8.7 ± 7.9 days after visit 1. Following exercise, 29/48 patients (60.4%) with NC had a decline of ≥12% in forced expiratory volume in the first second (FEV1 ) (positive ECT) compared to only 16/48 (33.3%) positive tests without NC (p = 0.0008). Test result was changed in 14 patients from positive ECT (with NC) to negative ECT (no NC) and in only one patient from negative to positive. The use of NC resulted in greater FEV1 decline (median 16.3% predicted, IQR 6.0-19.1% predicted vs. median 4.5% predicted, IQR 1.6-18.4% predicted, p = 0.0001), and better FEV1 increase after bronchodil at or inhalation compared to ECT without NC. Higher TNSS scores did not predict higher probability to positive ECT. CONCLUSIONS: The use of NC during ECT increases detection rate of exercise induced bronchoconstriction during ECT in the pediatric population. These findings strengthen the recommendation of nasal blockage during ECT in children and adolescents.

Establishing an everyday scientific reasoning scale to learn how non-scientists reason with science.

Scientific concepts and core ideas are fundamental for scientific inquiry and research. However, they are not always understood by non-scientists who encounter science in the media, conversations with friends, and other daily contexts. To assess how non-scientists reason with science in daily life, we extend the work described by Drummond and Fischhoff by developing an everyday scientific reasoning scale and demonstrating its ability to predict the use and application of daily scientific information. This article features three studies describing the development, validation, and use of the everyday scientific reasoning scale. Findings demonstrate an association between respondents' scores on the everyday science reasoning scale and their level of education and suggest that using daily scenarios for framing science facilitates the process of understanding scientific concepts. These results have important implications for communicating science in society and engaging diverse populations with science.

Characterization of acquired anemia in children by iron metabolism parameters.

Inflammatory states are associated with anemia of chronic disease and acute infection. Hepcidin, a regulator of iron metabolism, is involved in iron pathophysiology during inflammation. We investigated biochemical characteristics in children with anemia from different causes. Four patient groups (n = 38; mean age: 12.44 ± 4.35 years) were studied: (1) inflammatory bowel disease (IBD, 10 patients); (2) iron deficiency anemia (IDA, 12); (3) celiac disease (CD, 8); (4) acute infection (AI, 8). Laboratory measurements were evaluated at diagnosis: blood count, serum iron, transferrin, ferritin, vitamin B12, folic acid, CRP, erythropoietin, hepcidin and soluble transferrin receptor (sTfR). IDA patients had the lowest Hgb (6.9 ± 1.7 g/dL), MCV (63.2 ± 7.2 fL), iron (16.8 ± 13.5 µg/dL), ferritin (4.5 ± 4.5 ng/mL) and hepcidin (3.1 ± 0.8 ng/mL) values, and the highest transferrin and sTfR values. AI patients had the highest ferritin (156.2 ± 124.5 ng/mL), CRP (144.6 ± 94 mg/L) and hepcidin (74.67 ± 12.3 ng/ml) values. Overall, hepcidin levels correlated with CRP and with ferritin (r = 0.83 and 0.85, respectively). Elucidating specific etiology-related biochemical profiles in pediatric patients with anemia from different causes using a combination of laboratory biomarkers, including hepcidin, can help physicians treat the anemia.

Lost in the matrix: Dialectical tensions in facilitating virtual video groups during COVID-19 pandemic.

The research phenomenologically explored the experience of facilitating virtual video groups during the COVID-19 pandemic. Research questions addressed relational processes in virtual video groups, including emotional presence, interpersonal communication, and intimacy. Specifically, we asked how facilitators can intervene effectively to promote these processes in the virtual space, within the context of social distancing. Semi-structured group interviews were held with 26 female group facilitators from various professional backgrounds during the first wave of COVID-19 in Israel in May 2020. Phenomenological analysis yielded five main themes addressing dialectical tensions that operate simultaneously in the virtual space, both enabling and hindering relational processes in virtual video groups: intimacy and intrusion in the domestic space; sharp transitions from presence to absence; fragmented processing despite abundant information; sterility and clarity in group communication; and the hyper-aware self - being a participant and an observer at the same time. Moving groups into a virtual sphere challenged the traditional role of facilitators, who struggled to create a safe space in an unstable virtual setting where the boundaries between personal and professional lives were reduced. Findings also point to the potential of the domestic space to promote closeness and intimacy and suggest the virtual space requires facilitators to embrace multiplicity as a state of mind when intervening. Facilitators must work with permeable boundaries between inner and outer group spaces, accept discontinuity as a basic property of the virtual, and acknowledge the limitations caused by multiple stimuli.

The Association between IgG and Disease Severity Parameters in CF Patients.

Assessing disease severity in patients with cystic fibrosis (CF) is essential when directing therapies. Serum immunoglobulin G (IgG) levels increase with disease severity. Lung clearance index (LCI) is recognized as an outcome measure for CF clinical trials. Our aim was to evaluate the correlations between IgG and disease severity markers. This was a single-center retrospective study, evaluating association between IgG and markers of severity in CF patients (including clinical characteristics, lung spirometry, LCI, clinical scores and computed tomography (CT) scores) during stable conditions. There were 69 patients, age 20.5 ± 11.6 years. Nineteen (27.5%) patients had elevated IgG. IgG correlated positively with LCI (r = 0.342, p = 0.005). IgG was higher in pancreatic insufficient (PI) and patients with liver disease (1504.3 ± 625.5 vs. 1229 ± 276.1 mg/dL in PI vs. PS, p = 0.023, and 1702.6 ± 720.3 vs. 1256.2 ± 345.5 mg/dL with vs. without liver disease, p = 0.001, respectively). IgG also correlated positively with CRP, CT score, and days with antibiotics in the previous year (r = 0.38, p = 0.003; r = 0.435, p = 0.001; and r = 0.361, p = 0.002, respectively), and negatively with FEV1% and SK score (r = -0.527, p < 0.001 and r = -0.613, p < 0.001, respectively). IgG correlated with clinical parameters, pulmonary functions, and imaging. However, this is still an auxiliary test, complementing other tests, including lung function and imaging tests. Larger multi-center longitudinal studies are warranted.

Reverse butterfly pattern image with eosinophilia: Effective treatment with benralizumab-A case report.

A 16-year-old adolescent presented with dry cough, fever, weight loss, night sweats, exercise intolerance, and eosinophilia. Computed tomography showed consolidations with "reverse butterfly" pattern. He responded well to corticosteroids but had frequent relapses. He became steroid dependent and developed steroid related morbidity. Benralizumab was prescribed with complete resolution of eosinophilia and lung infiltrates with no adverse effect.

Suppression of neuroinflammation by an allosteric agonist and positive allosteric modulator of the α7 nicotinic acetylcholine receptor GAT107.

BACKGROUND: The α7 nicotinic acetylcholine receptor (α7 nAChR) negatively regulates the synthesis and release of pro-inflammatory cytokines by immune cells. Our previous studies showed that in encephalitogenic T cells, α7 nAChR expression is upregulated and that activation of the cholinergic system can attenuate experimental autoimmune encephalomyelitis (EAE). GAT107 is an allosteric agonist and positive allosteric modulator (ago-PAM) of α7 nAChR that can produce persistent activation of this receptor. Therefore, in the present study, we investigated the effect of GAT107 on neuroinflammation in EAE, the animal model used for the study of multiple sclerosis (MS) via α7 nAChR, and the inflammatory pathways involved. METHODS: EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG35-55) in C57BL/6 mice. EAE mice were treated with the ago-PAM GAT107 or a placebo for 9 days, starting from the day of EAE induction. Clinical assessment and immunological evaluation of immune cells and cytokine production was performed. RESULTS: Following activation of the α7 nAChR by GAT107 during EAE, disease severity was significantly reduced by 70% and was correlated with a reduction in the extent of neuroinflammation in the CNS. The treatment reduced encephalitogenic T cell proliferation and the production of pro-inflammatory cytokines, as well as increased the production of the anti-inflammatory cytokine IL-10. Furthermore, the expression of immune cell markers was altered by GAT107 treatment, which induced a significant reduction in macrophages, dendritic cells, and B cells, as well as a reduction in anti-MOG35-55 antibodies. Additionally, GAT107 was found to directly activate α7 nAChR in murine macrophage RAW264.7 cells and in human PBMCs derived from MS patients and healthy donors. CONCLUSIONS: Our results show that GAT107 can be a useful molecule for harnessing the cholinergic anti-inflammatory pathway for long-lasting and wide-ranging modulation and downregulation of neuroinflammation in EAE.

Atypical cardiopulmonary manifestations in pediatric Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a multisystem autoinflammatory disease of unknown etiology. Cardiopulmonary involvement is rare, especially in young patients, and carries high morbidity and mortality rates. AIM: Of 26 patients with pediatric BD enlisted in our center, we encountered three patients with severe atypical cardiorespiratory presentations. Our aim was to describe the manifestations and the course that led to the diagnosis of BD. RESULTS: Three adolescents presented with intracardiac thrombi and left anterior descending obstruction causing myocardial infarction, pulmonary artery aneurysm with pulmonary embolism in situ, and suspected epiglottitis. Two patients had a delayed diagnosis of BD, and all had a good response to anti-inflammatory agents. CONCLUSIONS: This study demonstrated that pediatric BD is associated with atypical cardiopulmonary manifestations which maybe life threatening. Since diagnosis maybe challenging, a high index of suspicion is needed especially in young patients, to promptly diagnose and treat these complications. Cardiopulmonary signs and symptoms, though uncommon, maybe the first manifestation and a clue to the diagnosis of this rare disease.

RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels having many functions including inflammation control, as part of the cholinergic anti-inflammatory pathway. Genome wide association studies implicated RIC3, a chaperone of nAChRs, in multiple sclerosis (MS), a neuroinflammatory disease. To understand the involvement of RIC3 in inflammatory diseases we examined its expression, regulation, and function in activated immune cells. Our results show that immune activation leads to dynamic changes in RIC3 expression, in a mouse model of MS and in human lymphocytes and macrophages. We also show similarities in the expression dynamics of RIC3 and CHRNA7, encoding for the α7 nAChR subunit. Homomeric α7 nAChRs were shown to mediate the anti-inflammatory effects of cholinergic agonists. Thus, similarity in expression dynamics between RIC3 and CHRNA7 is suggestive of functional concordance. Indeed, siRNA mediated silencing of RIC3 in a mouse macrophage cell line eliminates the anti-inflammatory effects of cholinergic agonists. Furthermore, we show increased average expression of RIC3 and CHRNA7 in lymphocytes from MS patients, and a strong correlation between expression levels of these two genes in MS patients but not in healthy donors. Together, our results are consistent with a role for RIC3 and for the mechanisms regulating its expression in inflammatory processes and in neuroinflammatory diseases.

Can scientists fill the science journalism void? Online public engagement with science stories authored by scientists.

In many countries the public's main source of information about science and technology is the mass media. Unfortunately, in recent years traditional journalism has experienced a collapse, and science journalism has been a major casualty. One potential remedy is to encourage scientists to write for news media about science. On these general news platforms, scientists' stories would have to compete for attention with other news stories on hard (e.g. politics) and entertaining (e.g. celebrity news) topics written by professional writers. Do they stand a chance? This study aimed to quantitatively characterize audience interactions as an indicator of interest in science news stories authored by early career scientists (henceforth 'scientists') trained to function as science reporters, as compared to news items written by reporters and published in the same news outlets. To measure users' behavior, we collected data on the number of clicks, likes, comments and average time spent on page. The sample was composed of 150 science items written by 50 scientists trained to contribute popular science stories in the Davidson Institute of Science Education reporters' program and published on two major Israeli news websites-Mako and Ynet between July 2015 to January 2018. Each science item was paired with another item written by the website's organic reporter, and published on the same channel as the science story (e.g., tourism, health) and the same close time. Overall significant differences were not found in the public's engagement with the different items. Although, on one website there was a significant difference on two out of four engagement types, the second website did not have any difference, e.g., people did not click, like or comment more on items written by organic reporters than on the stories written by scientists. This creates an optimistic starting point for filling the science news void by scientists as science reporters.

Factors predicting length of stay in bronchiolitis.

INTRODUCTION: Despite advances in medical knowledge, the treatment of viral bronchiolitis is mainly supportive. Antiviral therapies are being investigated in clinical trials. Identifying population-attributable risk factors for RSV hospitalization may help prioritizing targeted treatment. AIM: To utilize MDClone, a data acquisition tool, to examine factors associated with the risk of hospitalization and length of stay (LOS) in bronchiolitis. METHODS: A single tertiary medical center retrospective study. Infants discharged with a diagnosis of bronchiolitis between January 2001 and March 2019 were included. Demographic, clinical, laboratory, microbiologic parameters and co-morbidities were collected. Correlations with the risk of hospitalization and LOS were examined. RESULTS: A total of 4793 infants with bronchiolitis, 3851 (80.3%) previously healthy, were seen; 975 visited emergency room only; 3311 were hospitalized in pediatric wards and 507 required pediatric intensive care unit. O2 saturation, age and fever correlated with the risk of hospitalization (OR = 0.703, p < 0.0001, OR = 0.4, p = 0.024 and OR = 2.388, p < 0.0001, respectively). Saturation, fever, gestational age and birth weight correlated with LOS (r = -0.283, p = 0.000; r = 0.16, p = 0.000; r = -0.12, p = 0.00; and r = -0.117, p = 0.00, respectively). Rates of hospitalization were higher (81.1% vs. 75.6%, p = 0.0008) and LOS was longer (median 2.97 vs. 2.73 days, p < 0.001) in Arabs than in Jews. In a multivariate model, saturation, fever, gestational age and age predicted LOS. Saturation and ethnicity predicted LOS for previously healthy infants. Prematurity and cardiac anomalies increased LOS (p = 0.016 and p < 0.0001, respectively). CONCLUSIONS: Population-based data may enable predicting disease severity and LOS in bronchiolitis. Focusing on children at greatest risk may aid targeting new therapies.

The utility of next generation sequencing in the correct diagnosis of congenital hypochloremic hypokalemic metabolic alkalosis.

Persistent hypokalemic hypochloremic metabolic alkalosis represents a heterogeneous group of genetic disorders of which the most common is Bartter syndrome (BS). BS is an inherited renal tubulopathy caused by defective salt reabsorption in the thick ascending loop of Henle, which results in persistent hypokalemic hypochloremic metabolic alkalosis. Here we report a 10-year-old girl of a consanguineous family. She presented prenatally with severe polyhydramnios and distended bowel loops. Thereafter, she displayed failure to thrive and had recurrent admissions due to dehydration episodes associated with diarrhea, and characterized by hypokalemia, hypochloremia and metabolic alkalosis. BS was considered her working diagnosis for several years despite negative genetic analysis of the known genes associated with BS. Whole exome sequencing identified a novel homozygous c.1652delT deleterious frameshift mutation in the SLC26A3 gene, which confirmed the diagnosis of congenital chloride diarrhea (CCD), a rare autosomal recessive disease that mimics biochemically BS. A review of twelve additional reported cases of CCD that were initially misdiagnosed as BS, emphasizes CCD in the differential diagnosis of BS, and highlights the clinical discrepancies between these two entities. Taken together, our report further emphasizes the typical clinical features of CCD, and the importance of next generation sequencing in the diagnosis of syndromes with genetic heterogeneity. We suggest including SLC26A3 in the extended BS targeted gene panels.

Role of the α7 Nicotinic Acetylcholine Receptor and RIC-3 in the Cholinergic Anti-inflammatory Pathway.

BACKGROUND: The nicotinic acetylcholine receptor (nAChR) gene family encodes for subunits of acetylcholine gated ion channels. These receptors are expressed widely and have many functions: They mediate excitation at neuro-muscular junctions. Nicotinic Acetylcholine Receptor: In the central nervous system nAChRs have been implicated in memory, cognition, and addiction. And in non-excitatory cells they regulate differentiation, proliferation and inflammatory responses. The CHRNA7 gene encodes for the α7 nAChR subunit that assembles into a homomeric receptor having unusual properties. It is expressed widely and has many functions atypical for nAChRs; specifically, in immune cells α7 is required for the anti-inflammatory effects of acetylcholine and has been implicated in inflammatory autoimmune diseases including Multiple Sclerosis (MS). Interestingly, although, α7 receptors are found at the outer membranes of immune cells, acetylcholine-dependent currents have not been recorded from these cells. Therefore, its mechanism of action in immune cells needs further evaluation. Maturation of α7 into functional ligand-gated channels in the plasma membrane is a complex process shown to depend on the ER-resident chaperone, RIC-3. Therefore, RIC-3 regulates functional expression of α7. RIC-3 like α7 is expressed in immune cells and has been implicated in MS. Thus, RIC-3 may regulate functional expression of α7 in immune cells. CONCLUSION: In this review we describe effects and mechanism of action of α7 nAChR and RIC-3 in the immune cholinergic system. Elucidating these mechanisms and the regulation of α7 and RIC-3 in the immune cholinergic system can pave the way for novel immunomodulatory agents, or towards extending the application of cholinergic agents.

RIC-3 expression and splicing regulate nAChR functional expression.

BACKGROUND: The nicotinic acetylcholine receptors form a large and diverse family of acetylcholine gated ion channels having diverse roles in the central nervous system. Maturation of nicotinic acetylcholine receptors is a complex and inefficient process requiring assistance from multiple cellular factors including RIC-3, a functionally conserved endoplasmic reticulum-resident protein and nicotinic acetylcholine receptor-specific chaperone. In mammals and in Drosophila melanogaster RIC-3 is alternatively spliced to produce multiple isoforms. RESULTS: We used electrophysiological analysis in Xenopus laevis oocytes, in situ hybridization, and quantitative real-time polymerase chain reaction assays to investigate regulation of RIC-3's expression and splicing and its effects on the expression of three major neuronal nicotinic acetylcholine receptors. We found that RIC-3 expression level and splicing affect nicotinic acetylcholine receptor functional expression and that two conserved RIC-3 isoforms express in the brain differentially. Moreover, in immune cells RIC-3 expression and splicing are regulated by inflammatory signals. CONCLUSIONS: Regulation of expression level and splicing of RIC-3 in brain and in immune cells following inflammation enables regulation of nicotinic acetylcholine receptor functional expression. Specifically, in immune cells such regulation via effects on α7 nicotinic acetylcholine receptor, known to function in the cholinergic anti-inflammatory pathway, may have a role in neuroinflammatory diseases.

Defensive helping: threat to group identity, ingroup identification, status stability, and common group identity as determinants of intergroup help-giving.

On the basis of development of the concept of "defensive helping," the authors demonstrated that high ingroup identifiers thwart a threat to group identity through defensive help-giving (i.e., by extending help to an outgroup member whose achievements jeopardize their status). Participants were 255 Israeli high school students (130 boys and 125 girls) ages 16-18. The phenomenon of defensive helping was demonstrated in a minimal group (Study 1) and real-group (Study 2) experiment. Study 3, which examined real groups, supported the extension of the phenomenon of defensive helping to relations between high- and low-status groups, showing that members of a high-status group who perceive status relations with the low-status outgroup as unstable will protect the ingroup's identity by providing dependency-oriented help to the low-status outgroup. Priming for common ingroup identity reversed this pattern, with participants electing to offer autonomy-oriented rather than defensive help. Theoretical and applied implications of these findings are discussed with respect to social change, paternalism, and helping between nations.