To study whether early postnatal (<12 hours) dexamethasone therapy reduces the incidence of chronic lung disease in preterm infants with respiratory distress syndrome.
A multicenter randomized, ...double-blind clinical trial was undertaken on 262 (saline placebo, 130; dexamethasone, 132) preterm infants (<2000 g) who had respiratory distress syndrome and required mechanical ventilation shortly after birth. The sample size was calculated based on the 50% reduction in the incidence of chronic lung disease when early dexamethasone is used, allowing a 5% chance of a type I error and a 10% chance of a type II error. For infants who received dexamethasone, the dosing schedules were: 0.25 mg/kg/dose every 12 hours intravenously on days 1 through 7; 0.12 mg/kg/dose every 12 hours intravenously on days 8 through 14; 0.05 mg/kg/dose every 12 hours intravenously on days 15 through 21; and 0. 02 mg/kg/dose every 12 hours intravenously on days 22 through 28. A standard protocol for respiratory care was followed by the participating hospitals. The protocol emphasized the criteria of initiation and weaning from mechanical ventilation. The diagnosis of chronic lung disease based on oxygen dependence and abnormal chest roentgenogram was made at 28 days of age. To assess the effect of dexamethasone on pulmonary inflammatory response, serial tracheal aspirates were assayed for cell counts, protein, leukotriene B4, and 6-keto prostaglandin F1alpha. All infants were observed for possible side effects, including hypertension, hyperglycemia, sepsis, intraventricular hemorrhage, retinopathy of prematurity, cardiomyopathy, and alterations in calcium homeostasis, protein metabolism, and somatic growth.
Infants in the dexamethasone group had a significantly lower incidence of chronic lung disease than infants in the placebo group either judged at 28 postnatal days (21/132 vs 40/130) or at 36 postconceptional weeks (20/132 vs 37/130). More infants in the dexamethasone group than in the placebo group were extubated during the study. There was no difference between the groups in mortality (39/130 vs 44/132); however, a higher proportion of infants in the dexamethasone group died in the late study period, probably attributable to infection or sepsis. There was no difference between the groups in duration of oxygen therapy and hospitalization. Early postnatal use of dexamethasone was associated with a significant decrease in tracheal aspirate cell counts, protein, leukotriene B4, and 6-keto prostaglandin F1alpha, suggesting a suppression of pulmonary inflammatory response. Significantly more infants in the dexamethasone group than in the placebo group had either bacteremia or clinical sepsis (43/132 vs 27/130). Other immediate, but transient, side effects observed in the dexamethasone group are: an increase in blood glucose and blood pressure, cardiac hypertrophy, hyperparathyroidism, and a transient delay in the rate of growth.
In preterm infants with severe respiratory distress syndrome requiring assisted ventilation shortly after birth, early postnatal dexamethasone therapy reduces the incidence of chronic lung disease, probably on the basis of decreasing the pulmonary inflammatory process during the early neonatal period. Infection or sepsis is the major side effect that may affect the immediate outcome. Other observable side effects are transient. In view of the significant side effects and the lack of overall improvement in outcome and mortality, and the lack of long term follow-up data, the routine use of early dexamethasone therapy is not yet recommended.
The intestinal epithelium compartmentalizes the sterile bloodstream and the commensal bacteria in the gut. Accumulating evidence suggests that this barrier is impaired in sepsis, aggravating systemic ...inflammation. Previous studies reported that cathelicidin is differentially expressed in various tissues in sepsis. However, its role in sepsis-induced intestinal barrier dysfunction has not been investigated.
To examine the role of cathelicidin in polymicrobial sepsis, cathelicidin wild-(Cnlp
) and knockout (Cnlp
) mice underwent cecal-ligation and puncture (CLP) followed by the assessment of septic mortality and morbidity as well as histological, biochemical, immunological, and transcriptomic analyses in the ileal tissues. We also evaluated the prophylactic and therapeutic efficacies of vitamin D3 (an inducer of endogenous cathelicidin) in the CLP-induced murine polymicrobial sepsis model.
The ileal expression of cathelicidin was increased by three-fold after CLP, peaking at 4 h. Knockout of Cnlp significantly increased 7-day mortality and was associated with a higher murine sepsis score. Alcian-blue staining revealed a reduced number of mucin-positive goblet cells, accompanied by reduced mucin expression. Increased number of apoptotic cells and cleavage of caspase-3 were observed. Cnlp deletion increased intestinal permeability to 4kD fluorescein-labeled dextran and reduced the expression of tight junction proteins claudin-1 and occludin. Notably, circulating bacterial DNA load increased more than two-fold. Transcriptome analysis revealed upregulation of cytokine/inflammatory pathway. Depletion of Cnlp induced more M1 macrophages and neutrophils compared with the wild-type mice after CLP. Mice pre-treated with cholecalciferol (an inactive form of vitamin D3) or treated with 1alpha, 25-dihydroxyvitamin D3 (an active form of VD3) had decreased 7-day mortality and significantly less severe symptoms. Intriguingly, the administration of cholecalciferol after CLP led to worsened 7-day mortality and the associated symptoms.
Endogenous cathelicidin promotes intestinal barrier integrity accompanied by modulating the infiltration of neutrophils and macrophages in polymicrobial sepsis. Our data suggested that 1alpha, 25-dihydroxyvitamin D3 but not cholecalciferol is a potential therapeutic agent for treating sepsis.
Spatially-resolved electroluminescence (EL) images in the triple-junction InGaP/InGaAs/Ge solar cell have been investigated to demonstrate the subcell coupling effect. Upon irradiating the infrared ...light with an energy below bandgap of the active layer in the top subcell, but above that in the middle subcell, the EL of the top subcell quenches. By analysis of EL intensity as a function of irradiation level, it is found that the coupled p-n junction structure and the photovoltaic effect are responsible for the observed EL quenching. With optical coupling and photoswitching effects in the multi-junction diode, a concept of infrared image sensors is proposed.
The global ionospheric map (GIM) is used to observe variations in the total electron content (TEC) of the global positioning system (GPS) associated with 35 M ≥ 6.0 earthquakes that occurred in China ...during the 10‐year period of 1 May 1998 to 30 April 2008. The statistical result indicates that the GPS TEC above the epicenter often pronouncedly decreases on day 3–5 before 17 M ≥ 6.3 earthquakes. The GPS TEC of the GIM and electron density profiles probed by six microsatellites of FORMOSAT3/COSMIC (F3/C) are further employed to simultaneously observe seismoionospheric anomalies during an Mw7.9 earthquake near Wenchuan, China, on 12 May 2008. It is found that GPS TEC above the forthcoming epicenter anomalously decreases in the afternoon period of day 6–4 and in the late evening period of day 3 before the earthquake, but enhances in the afternoon of day 3 before the earthquake. The spatial distributions of the anomalous and extreme reductions and enhancements indicate that the earthquake preparation area is about 1650 km and 2850 km from the epicenter in the latitudinal and longitudinal directions, respectively. The F3/C results further show that the ionospheric F2 peak electron density, NmF2, and height, hmF2, significantly decreases approximately 40% and descends about 50–80 km, respectively, when the GPS TEC anomalously reduces.
Although treatment of brain abscess requires a combination of antimicrobials and surgical intervention for the infected foci, nonsurgical, empirical treatment is possible and efficient in selected ...groups of patients. A total of 31 patients were enrolled in this 22-year retrospective study. We describe our therapeutic experiences and attempt to analyze the risk factors that were predictive of therapeutic outcomes. Multiple logistic regression was used to evaluate the relationships between baseline clinical factors and therapeutic outcome during the study period. Of these 31 patients, 25 had community-acquired infections, whereas the other six had nosocomially-acquired infections. Thirteen cases (42%) had a single brain abscess and the other 18 cases (58%) had multiple brain abscesses. Furthermore, the association of bacterial meningitis and brain abscess was found in 81% (25/31) of cases. The overall case fatality rate was 48% (15/31). Significant risk factors for poor outcomes included Glasgow coma scale (GCS) at presentation, presence of septic shock and neck stiffness. In addition, each reduction of one point on the GCS increased the poor outcome rate by 28%. The findings of the study demonstrate that both a higher mortality rate (48%) and worse outcomes were found in this select group of patients. Among the significant prognostic factors, a lower mean GCS at presentation was a major determinant of poor outcome.
Malignant pleural effusion (MPE) accompanying lung adenocarcinoma indicates poor prognosis and early metastasis. This study aimed to identify genes related to MPE formation. Three tissue sample ...cohorts, seven from healthy lungs, 18 from stage I-III lung adenocarcinoma with adjacent healthy lung tissue and 13 from lung adenocarcinomas with MPE, were analysed by oligonucleotide microarray. The identified genes were verified by quantitative real-time PCR (qRT-PCR), immunohistochemical staining, and immunofluorescence confocal microscopy. 20 up- or down-regulated genes with a two-fold change in MPE cancer cells compared to healthy tissues were differentially expressed from early- to late-stage lung cancer. Of 13 genes related to cellular metabolism, aldolase A (ALDOA), sorbitol dehydrogenase (SORD), transketolase (TKT), and tuberous sclerosis 1 (TSC1) were related to glucose metabolism. qRT-PCR validated their mRNA expressions in pleural metastatic samples. Immunohistochemical staining confirmed aberrant TKT, ALDOA, and TSC1 expressions in tumour cells. Immunofluorescence confirmed TKT co-localisation and co-distribution of ALDOA with thyroid transcription factor 1-positive cancer cells. TKT regulated the proliferation, vascular endothelial growth factor secretion in vitro and in vivo vascular permeability of cancer cell. Glucose metabolic reprogramming by ALDOA, SORD, TKT and TSC1 is important in MPE pathogenesis.
The optimal strategy of chroma 422 subsampling for Bayer pattern in H.264 video coding is proposed. The state-of-the-art work uses a predetermined conversion method from colour filter array to YCbCr ...422. Derived from this structure, first, 64 subsampling methods are designed to exploit more possibilities. Secondly, among which, the four optimal methods are found by the pre-screening process, which show their better performances than the state-of-the-art method by up to 2.57 dB in CPSNR averaged for different videos, demonstrating the practicability of the proposed methods. Finally, for the experiment consisting of the whole conversion and H.264 video encoding/decoding procedures, the proposed optimal methods perform better than the state-of-the-art method under all different operating bitrates and different tested videos, by up to 2.25 dB in BDPSNR.
Background
Multiple mechanisms contribute to the stimulus‐evoked pain hypersensitivity that may be experienced after peripheral inflammation. Persistent pathological stimuli in many pain conditions ...affect the expression of certain genes through epigenetic alternations. The main purpose of our study was to investigate the role of epigenetic modification on potassium‐chloride co‐transporter 2 (KCC2) gene expression in the persistence of inflammatory pain.
Methods
Persistent inflammatory pain was induced through the injection of complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl‐histone H3 and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal horn. Pain behaviour and inhibitory synaptic function of spinal cord were determined before and after CFA injection. KCC2 expression was determined by real time RT‐PCR and Western blot. Intrathecal KCC2 siRNA (2 μg per 10 μL per rat) or HDAC inhibitor (10 μg per 10 μL per rat) was injected once daily for 3 days before CFA injection.
Results
Persistent inflammatory pain epigenetically suppressed KCC2 expression through histone deacetylase (HDAC)‐mediated histone hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2 knock‐down caused by intrathecal administration of KCC2 siRNA in naïve rats reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours and impaired inhibitory synaptic transmission in their spinal cords. Moreover, intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression, partially restoring the spinal inhibitory synaptic transmission and relieving the sensitized pain behaviour.
Conclusion
These findings suggest that the transcription of spinal KCC2 is regulated by histone acetylation epigenetically following CFA.
Significance
Persistent pain suppresses KCC2 expression through HDAC‐mediated histone hypoacetylation and consequently impairs the inhibitory function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress the influences of persistent pain on the expression of KCC2 may serve as a novel analgesic.
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