Reading the unique DNA methylation landscape of the brain: Non-CpG methylation,hydroxymethylation, and MeCP2

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.     

Serological Responses of Raccoons and Striped Skunks to Ontario Rabies Vaccine Bait in West Virginia during 2012–2016

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.     

A new bioabsorbable sleeve for lung staple-line reinforcement (FOREseal™): report of a three-center phase II clinical trial

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.     

Hospital Episode Statistics and trends in ophthalmic surgery 1998 – 2004

Background  

Hospital episode statistics (HES) is a UK national database for the National Health Service (NHS), now available online. The purpose of this study was to observe trends in ophthalmic operations performed during the period from 1998 to 2004, using this data.     

Long-term surgical results for congenital aural atresia

Thirty-nine primary surgical cases for correction of congenital aural atresia were reviewed for complications and long-term hearing results. Hearing averages of 25 dB for mild atresia, 40 dB for moderate atresia, and 46 dB for severe atresia were obtained. Serviceable hearing was achieved in 64% of the cases. The two most frequent complications were stenosis and recurrent infections of the cavity and canal skin, with an incidence of 33% and 31%, respectively. Use of split-thickness instead of full-thickness skin graft was associated with fewer complications. The goal of this review is also to share the experience of the senior author in the management of this complex problem.     

Intimal hyperplasia and coronary flow reserve after heart transplantation: association with big endothelin-1

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.     

Attentional demands of continuously monitoring orientation using vestibular information.

The aim of this series of experiments was to determine whether attention is normally required for continuously processing vestibular information concerning orientation, or is required only when orientation is disrupted (eg by vestibular dysfunction or by conflicting visual and vestibular orientation cues). In the first two studies, healthy subjects were passively oscillated, and indicated when they perceived they were passing through their starting position. There was only weak evidence for interference between performance on this 'continuous orientation monitoring task' and on concurrent mental tasks. However, a third study showed that when patients with vestibular imbalance carried out the continuous orientation monitoring task their performance on a concurrent mental arithmetic task was substantially impaired. This dual task interference was correlated with inaccuracy in judging orientation on the continuous orientation monitoring task, which in turn correlated with severity of recent vestibular symptomatology (assessed by questionnaire). In a fourth experiment, disorientation was induced in healthy subjects by rotating the visual field about the line of sight. Bidirectional interference was observed between monitoring orientation (assessed by accuracy in setting a rod to the perceived vertical) and performance of an arithmetic task. Dual task interference was correlated with baseline levels of disorientation induced by the visual field, as indicated by inaccuracy in judging the visual vertical. These findings suggest that monitoring orientation makes significant demands upon cortical processing resources when disorientation is induced, whether the disorientation results from deficient sensory functioning or from ambiguous perceptual information.