Protein-losing enteropathy (PLE), defined as the abnormal loss of protein from the gastrointestinal tract, occurs in many diseases through pathologic processes that involve the enteric, vascular, and lymphatic systems. The cardinal features of PLE are edema and hypoalbuminemia, lymphopenia, and loss of T cells and immunoglobulins. Asymmetric peripheral edema may signify a lymph disorder that precedes PLE. Growth retardation is common in chronic cases of PLE. In general, manifestations are variable and depend on the underlying disease processes. The Fontan procedure is a well-known precursor of PLE, which sometimes appears years after the procedure itself. Erosion, ulceration, and inflammation of the intestinal mucosa causing PLE may be the result of infectious or noninfectious disorders. PLE is very occasionally a feature associated with cow's milk protein allergy. A child with edema and hypoalbuminemia, who is otherwise well-nourished and who does not have renal or liver disease, should undergo evaluation for PLE.
Chronic rhinosinusitis (CRS) shares a common pathophysiology with other chronic inflammatory diseases, including periodic acute exacerbations and altered wound-healing processes [1]. A healthy sinonasal mucosal barrier relies on immune function to appropriately respond to airborne insults while choreographing a temporally regulated resolution of the acute physiological inflammatory response [2]. When this spatiotemporal response is disrupted, chronic inflammation may result as a potential contribution to etiopathogenesis or sustenance of inflammation in CRS. Nuclear factor-kappa B (NF-κB) signaling is one of several important contributors in the modulation of important inflammatory responses. It is recognized as an important transcription factor in the expression of various pro-inflammatory genes in chronic inflammatory diseases including CRS [3]. Chronic inflammation occurring in nasal polyp tissues also contains some degree of active tissue inflammatory resolution in epithelial and immune cell populations. Specialized pro-resolving mediators, such as resolvin D2, may mitigate inflammatory responses initiated by lipopolysaccharide exposure. Active inflammation resolution is a novel approach to chronic rhinosinusitis (CRS) management, and more research is required to examine cell-specific temporal effects of specialized-pro-resolving mediators in CRS tissues. Lipid-derived molecules known as specialized-pro-resolving mediators (SPMs) [4] have recently been described as active components in temporal modulation of acute airway inflammatory responses and may play some role in the CRS disease process [5-7]. SPMs influence development, recruitment, and function of several inflammatory cells, including macrophages, dendritic cells, neutrophils, and lymphocytes [8]. In this study, we seek to understand SPM regulatory effects on NF-κB-associated pro-inflammatory genes using a fresh sinus tissue explant model. We hypothesize that SPM, resolvin D2 (RvD2), will mitigate lipopolysaccharide (LPS)-induced inflammation. Nasal polyp tissue was obtained via endoscopic sinus surgery at Indiana University School of Medicine (IRB #14784). Nasal polyp tissues were obtained from three subjects. All of these patients had clinical features of type 2 inflammatory disease, with either allergic rhinitis, asthma, or aspirin-exacerbated airway disease (Table S1). Tissues from the middle meatus and ethmoid sinus cavities were collected from patients. Upon harvest, specimens were immediately taken to the laboratory, serially rinsed with phosphate-buffered saline (PBS), and gently centrifuged to remove excess blood and mucus. Tissues were then preserved in 1:1 PBS and 10% dimethyl sulfoxide in liquid nitrogen. When preparing for experimental exposures, tissue was thawed and weighed. Plates were filled with 0.04 g tissue in 1 mL culture medium. Each sample was exposed to 10 µg/mL LPS, 50 nM RvD2, and 10 µg/mL LPS + 50 nM RvD2, or exclusively culture medium for 24 h ± 1 h. Tissue RNA was extracted and isolated, then cDNA was synthesized using a reverse transcription kit according to standard manufacturer protocol (see Supporting Information for additional details). A microarray NF-κB panel was used to amplify cDNA by real-time PCR. Fold increase was compared to control via ∆∆CT method, and those with the most significant differences were selected as candidate genes for further validation. To validate the effects of RvD2 on gene expression, qPCR for selected gene products was applied for CXCL1, G-CSF, and MYD88 in triplicate. qPCR was utilized to quantitatively assess the production of RNA in each of these genes with the same tissue samples used in PCR microarray. Statistical analysis was performed using GraphPad Prism. A paired t-test was performed to test the effects of SPM treatment with RvD2 for each inflammatory mediator. Multiple comparisons correction was applied between groups, and an alpha <0.05 was set for statistical significance. In the NF-κB microarray, the physiologically relevant genes with the highest fold-changes after LPS exposure were MYD88, CXCL1, and G-CSF. RvD2 treatment was also found to significantly alter expression of these genes (Figure 1). QPCR validation illustrated that G-CSF expression increased in response to LPS stimulation and was abolished with RvD2 treatment (p < 0.01; Figure 2). MYD88 and CXCL-1 were inconsistent in their expression response patterns. CXCL-1 and MYD88 exhibited no significant increase in expression at 24 h with LPS exposure compared to control, limiting experimental potential for beneficial effects of RvD2 treatment on these target genes. CRS remains enigmatic in its pathophysiology, time course, and idiosyncratic responses to various treatments. Prior studies show that defects in the production of pro-resolving mediators, such as RvD2, have been implicated in the pathophysiology of airway disease [9]. Actions of pro-resolving mediators may offer a novel approach to treating the inflammatory processes that facilitate disease chronicity via attenuation of NF-κB effects in numerous cell types. In a PCR microarray, ex vivo polyp tissue treated with LPS for 24 h demonstrated a significant inflammatory response in G-CSF, MYD88, and CXCL1 expression, mitigated with concomitant RvD2 treatment. We attempted to validate the microarray results, and while MYD88 and CXCL1 showed an inconsistent response to LPS and RvD2, G-CSF expression pattern was convincing in its increase with LPS exposure and significant reduction with RvD2 treatment. G-CSF plays a vital role in innate immunity and inflammation by increasing the production and chemotaxis of neutrophils [10] and could be a biologically important target for SPMs in CRS. While this pilot investigation of RvD2 effects on inflammation in CRS tissues showed some interesting findings, further work is required. The small study size (n = 3) could be expanded to include subjects with more neutrophilic or mixed inflammatory disease, such as nonpolyp CRS or select CRSwNP cases. More cellular and molecular targets could be included, along with specific assessment of NF-κB activity. The inflammatory response is dependent on temporal regulation, and additional exposure time courses to pro-inflammatory stimuli, RvD2, and other SPMs could be tested. Lastly, we utilized a novel ex vivo tissue culture approach to include the numerous cell types involved in CRS, and further work is required to understand nuances of this experimental model, including a detailed understanding of the ex vivo maintenance and function of the various cell populations. This study establishes a potential effect of the specialized pro-resolving mediator, RvD2, in a CRS polyp tissue explant model. SPMs may elicit changes in gene expression that resolve active inflammation, including gene products that influence immune cell development and recruitment, and cytokines that direct acute phase responses. VRR has served as a consultant for Medtronic, Inc., and 3D-Matrix, which are unaffiliated with the current study. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The ongoing pursuit of mixed-dimensional van der Waals heterojunctions has attracted enormous interests owing to their obviously enhanced photoelectrochemical (PEC) characteristics compared to single component. Herein, we demonstrate the preparation of 0D Bismuth nanoparticles (Bi NPs) coated 2D Borophene (B@Bi) mixed-dimensional heterojunction by hydrothermal method. Density functional theory (DFT) calculations demonstrate that p-type Ohmic contact is formed between B and Bi. Benefiting from the promoted photo-induced electron/hole pair separation, shorted charge transfer length, and built-in electric field, the fabricated B@Bi-based PEC-type photodetector (PD) exhibits enhanced self-powered photodetection properties with a photocurrent of 954 nA cm -2 , a responsivity of 733.85 μA W -1 along with the fast response and recovery speed (0.02/0.02 s) in 0.5 M KOH electrolyte under 365 nm illumination. Additionally, repeatable ON/OFF switch signals could be observed after 30 days. Our present work provides an opportunity for fabricating high-performance mixed-dimensional B@Bi-based PDs with good long-term stability.
Metal organic chemical vapor deposited (MOCVD) thin films of aluminum nitride (AlN) were irradiated with 700 keV Ni ions at fluences of 1 × 1012, 1 × 1013, and 1 × 1014 ions cm−2. The stopping and range of ions in matter (SRIM) analysis was performed to investigate the depth distribution of the Ni ions and vacancy production in AlN film. The x-ray diffraction (XRD) patterns of the implanted samples show a shift of the AlN (0 0 2) orientation peak towards higher angles at 1 × 1012 ions cm−2, exhibiting the incorporation of nickel ions into the AlN phase. The XRD patterns also demonstrated a reduction in shift of the (0 0 2) orientation peak along with the formation of AlNi3 phase with the increase of ion fluence. The AFM surface analysis of the ion-irradiated AlN film exhibits a rise of film surface roughness. After ion irradiation, the samples were annealed at 900 °C in a nitrogen environment. Annealing reduces the surface roughness of not only the implanted samples but also the as-grown samples.
The aim of this research study was to investigate the relationship between career barriers, perceived professional social support and hopelessness level among female teachers of both private and public sectors. The research was quantitative in nature. An adapted questionnaire comprising of 45 close- ended statements was administered to a sample of 100 schoolteachers, 50 from public school and 50 from private secondary female school teachers in which there were 4 private schools and 4 public schools of Lahore. The sampling strategy used was convenience sampling. Parametric and non-parametric tests were used to examine the data. The study revealed no correlation between career barriers and feelings of hopelessness among private school teachers, although there was a strong relation between career barriers and professional social support among teachers. Among public school teachers, there was no significant relationship found between career barriers and both teacher professional social support and hopelessness levels. Furthermore, when comparing the three parameters between public and private school teachers, the findings revealed a significant difference in terms of career barriers between public and private school teachers. However, no significant difference was found in terms of teacher professional social support between private and public-school teachers. Additionally, there was statistically no significant difference between public and private school teachers in their hopelessness level. It is recommended that workshops, training sessions and seminars should be arranged to provide knowledge to both public and private school teachers about how to overcome career barriers.
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