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DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.  相似文献   
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Since the 1990s, oral rabies vaccination (ORV) has been used successfully to halt the westward spread of the raccoon rabies virus (RV) variant from the eastern continental USA. Elimination of raccoon RV from the eastern USA has proven challenging across targeted raccoon (Procyon lotor) and striped skunk (Mephitis mephitis) populations impacted by raccoon RV. Field trial evaluations of the Ontario Rabies Vaccine Bait (ONRAB) were initiated to expand ORV products available to meet the rabies management goal of raccoon RV elimination. This study describes the continuation of a 2011 trial in West Virginia. Our objective was to evaluate raccoon and skunk response to ORV occurring in West Virginia for an additional two years (2012–2013) at 75 baits/km2 followed by three years (2014–2016) of evaluation at 300 baits/km2. We measured the change in rabies virus-neutralizing antibody (RVNA) seroprevalence in targeted wildlife populations by comparing levels pre- and post-ORV during each year of study. The increase in bait density from 75/km2 to 300/km2 corresponded to an increase in average post-ORV seroprevalence for raccoon and skunk populations. Raccoon population RVNA levels increased from 53% (300/565, 95% CI: 50–57%) to 82.0% (596/727, 95% CI: 79–85%) during this study, and skunk population RVNA levels increased from 11% (8/72, 95% CI: 6–20%) to 39% (51/130, 95% CI: 31–48%). The RVNA seroprevalence pre-ORV demonstrated an increasing trend across study years for both bait densities and species, indicating that multiple years of ORV may be necessary to achieve and maintain RVNA seroprevalence in target wildlife populations for the control and elimination of raccoon RV in the eastern USA.  相似文献   
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Objective: To investigate on the feasibility, safety, and effectiveness of a new bioabsorbable material for lung staple-line reinforcement. Methods: This prospective open trial included 66 patients (mean age of 56 ± 17 years) who underwent various types of lung resection using staplers with knitted calcium alginate sleeves for buttressing (FOREseal™, Laboratoires Brothier, Nanterre, France) at three academic centers: 29 lobectomies, 22 emphysema surgeries, 15 wedge resections or lung biopsies. Intraoperative air leakage was assessed at a mean respiratory peak pressure of 30 cmH2O, and rated as grade 1, 2, or 3. Persistent air leakage in the postoperative course, as well as any relevant event, was assessed daily. The follow-up period was of 6 months. Results: No technical problem linked to the device occurred. Hemostasis of the cutting edges was completed in all patients. Fifty-six percent of the patients had no intraoperative air leak and 27.3% had grade 1 leaks. Mean postoperative air leaks and thoracic drainage times were 1.9 ± 2.3 days and 6 ± 5.3 days, respectively. In-hospital mortality was nil. There was no empyema. Mean hospital stay was 9.1 ± 6.6 days. At follow-up, one patient underwent lung transplantation, and pathology of the explanted specimen showed the absence of device-related foreign-body inflammation. One patient complained from metalloptysis, and another one, with a metastatic invasive aspergillosis, developed an infectious recurrence that required reoperation. Conclusions: FOREseal is an ergonomic, safe, and promising new material instead of nonabsorbable materials and xenomaterials for staple-line reinforcement. A randomized comparative study is now in progress.  相似文献   
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Critical care nurses within acute care settings are responsible for providing healthcare to a wide variety of patients and, consequently, knowledge regarding how to care for a patient with acute necrotizing fasciitis is imperative. A case study is presented to evidence the need for a multidisciplinary approach. Necrotizing fasciitis is defined and treatment options are presented. Caring for this patient is very challenging and demands a multidisciplinary team to coordinate all aspects of care to promote better patient outcomes.  相似文献   
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This study evaluates associations between soil lead concentrations (SPb), age of housing, and blood lead levels (BPb) of children in metropolitan New Orleans and Lafourche Parish, Louisiana. The database includes over 2,600 SPb and 6,000 BPb samples paired by their median values and pre-1940 housing percentages for 172 census tracts. Associations were evaluated with Fisher's exact test and Spearman's rho test and modeled with the least sum of absolute deviations regression. Census tracts with low SPb are associated with new housing, but census tracts with high SPb are evenly split between old and new housing [Fisher's exact test, p = 8.60 X 10(-13) for the percentage of housing built before 1940 (percent pre-1940 housing) versus SPb]. The p-value for SPb versus BPb is 12 orders of magnitude stronger than the p-value for percent pre-1940 housing versus BPb. Census tracts with low BPb are associated with new housing, but census tracts with high BPb are split evenly between old and new housing (Fisher's exact test, p = 1. 67 X 10(-12) for percent pre-1940 housing versus BPb). Census tracts with high SPb are associated with high BPb and census tracts with low SPb are associated with low BPb (Fisher's exact test, p = 3.18 X 10(-24) for BPb versus SPb). The Spearman's rho test of the association of SPb and BPb in Orleans and Lafourche Parishes yielded a p-value of 6.12 X 10(-24). The least sum of absolute deviations regression model of the data is BPb = 1. 845 + 0.7215 (SPb)0.4. A comparison of the modeled BPb versus observed BPb has an r(2) of 0.552 and a p-value of 2.83 X 10(-23) that this relation was due to chance. If blood lead in children is more closely associated to soil lead than to the age of housing, then primary lead prevention should also include soil lead.  相似文献   
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BACKGROUND: Endothelin, a peptide with strong vasoconstrictive and mitogenic properties, has been found to increase after cardiac transplantation. We therefore assessed the association between its precursor peptide, big endothelin-1, and intimal hyperplasia and coronary flow reserve after heart transplantation. METHODS: Thirty-five patients without hemodynamically significant coronary artery disease after heart transplantation were investigated: Average peak flow velocity in the left anterior descending artery (LAD) was assessed by intracoronary Doppler at baseline as well as after injection of adenosine; coronary flow reserve was calculated as a ratio of both and was corrected for patient age and baseline average peak flow velocity. Lumen, intima + media and total vessel area were measured by intracoronary ultrasound. The plasma concentration of big endothelin-1 in venous blood was determined by radioimmunoassay. RESULTS: Patients with elevated big endothelin-1 levels (>2 fmol/ml) tended to have a decreased corrected coronary flow reserve (2.60 +/- 0.9 vs 3.21 +/- 1.0, p = 0.078). They also had a significantly larger intima + media area (5.82 +/- 2.9 vs 2.37 +/- 2.9 mm(2), p = 0.004) and total vessel area (18.36 +/- 5.8 vs 12.81 +/- 4.8 mm(2), p = 0.012) than those with normal plasma concentrations. CONCLUSIONS: Our study suggests an association between elevated big endothelin-1 plasma levels and the development of intimal hyperplasia and reduction of coronary flow reserve after cardiac transplantation.  相似文献   
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Three-dimensional (3D) PET acquisition has the potential to reduce image noise but the advantage of 3D PET for studies outside the brain has not been well established. To compare the performance of 2-dimensional (2D) and 3D acquisition for whole-body (18)F-FDG applications, a series of patient studies were performed using a lutetium oxyorthosilicate (LSO)-based tomograph. METHODS: Comparative 2D and 3D images were acquired for 27 oncology patients using an LSO-based tomograph. Data acquisition (350-650 keV, 6 ns) started 99 +/- 12 min (mean +/- SD) after injection of 624 +/- 76 MBq (18)F-FDG. Bias caused by tracer redistribution and decay was eliminated by acquiring dynamic data over a single-bed position using a protocol that alternated between septa-in and septa-out modes (2D, 3D, 2D, 3D, 2D, 3D). Frames were combined to form 8 statistically independent sinograms: four 2D replicates (105 s) and four 3D replicates (90 s). The different frame durations in 2D and 3D compensated for the different number of overlapping bed positions required for an 85-cm whole-body study. Images were reconstructed with either 2D or fully 3D ordered-subsets expectation maximization (2 iterations and 8 subsets; 2D 6-mm gaussian, 3D 5- and 6-mm gaussian). Image target-to-background ratio was assessed by dividing the lesion maximum by the mean within a neighboring background region. Image noise was assessed by applying background regions of interest to the replicate images and calculating the within-patient coefficient of variation. RESULTS: The difference in target-to-background ratio between the 2D and 3D images, when they were filtered with 6-mm and 5-mm gaussian filters, respectively, was not highly statistically significant (P = 0.16). The mean ratio of 3D to 2D image values was 0.94 with 95% limits of agreement of 0.63-1.41. The within-patient coefficients of variation for the 2D and 3D images were 13% +/- 15% and 9% +/- 10%, respectively (P = 0.0005). CONCLUSION: Under conditions of matched target to-to-background ratios, the 3D mode was found to produce images with significantly less variability than the 2D mode. These data provide support for the use of 3D acquisition with LSO detectors to reduce scan times in whole-body (18)F-FDG applications.  相似文献   
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