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.     

Adductor Canal Block or Local Infiltrate Analgesia for Pain Control After Total Knee Arthroplasty? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Total knee arthroplasty is a treatment option for debilitating arthritis. In the postoperative period, patients experience moderate to severe pain affecting the rehabilitation, hospital stay, and patient satisfaction. This study aims at utilizing current best evidence to determine whether adductor canal block (ACB) or periarticular injection (PAI) is a better modality for managing short-term postoperative pain and opioid consumption.

Localizing a putative mutation as the major contributor to the development of sporadic Hirschsprung disease to the RET genomic sequence between the promoter region and exon 2

Hirschsprung disease (HSCR), a congenital disorder characterized by intestinal obstruction due to absence of enteric ganglia along variable lengths of the intestinal tract, occurs both in familial and sporadic cases. RET mutations have been found in approximately 50% of the families, but explains only a minority of sporadic cases. This study aims at investigating a possible role of RET in sporadic HSCR patients. Haplotypes of 13 DNA markers, within and flanking RET, have been determined for 117 sporadic HSCR patients and their parents. Strong association was observed for six markers in the 5' region of RET. The largest distortions in allele transmission were found at the same markers. One single haplotype composed of these six markers was present in 55.6% of patients versus 16.2% of controls. Odds ratios (ORs) revealed a highly increased risk of homozygotes for this haplotype to develop HSCR (OR>20). These results allowed us to conclude that RET plays a crucial role in HSCR even when no RET mutations are found. An unknown functional disease variant(s) with a dosage-dependent effect in HSCR is likely located between the promoter region and exon 2 of RET.     

Evaluating Differences in Whole Blood,Serum, and Urine Screening Tests for Zika Virus,Puerto Rico,USA, 2016

We evaluated nucleic acid amplification testing (NAAT) for Zika virus on whole-blood specimens compared with NAAT on serum and urine specimens among asymptomatic pregnant women during the 2015–2016 Puerto Rico Zika outbreak. Using NAAT, more infections were detected in serum and urine than in whole blood specimens.     

Factors That Predict 1-Year Incident Hip and Non-Hip Fractures for Home Care Recipients: A Linked-Data Retrospective Cohort Study

ObjectivesThe purpose of our study was to identify factors that predict 1-year incident hip and major osteoporotic non-hip fractures (ie, wrist, spine, pelvis, humerus) for home care recipients while accounting for the competing risk of death.DesignWe conducted a retrospective cohort study with linked population data.Setting and ParticipantsAll home care recipients in Ontario, Canada, receiving services for more than 6 months with an admission assessment between April 1, 2011, and March 31, 2015, were included.MethodsClinical data from the Resident Assessment Instrument Home Care were linked to fracture data from the Discharge Abstract Database and the National Acute Care Reporting System. Competing risk proportional hazard regressions using the Fine and Grey method were performed to model the association between potential risk factors and fracture.ResultsPrevious fall, previous fracture, cognitive impairment, unsteady gait, alcohol use, tobacco use, and Parkinson disease were consistently associated with all fracture types. Cognitive impairment (hazard ratio 2.09; 95% confidence interval 1.86–2.36) and wandering [1.66 (1.06–1.27)] were most predictive of hip fractures and being female [1.86 (1.76–1.98)] and experiencing a previous fracture [1.86 (1.76–1.98)] were most predictive of non-hip fractures. Risk factors unique to non-hip fractures as compared with hip fractures were locomotion ability outdoors and psychotropic medication use.Conclusions and ImplicationsOur results indicate that, in addition to typical fracture risk factors, home care recipients have unique characteristics that increase their risk. Fracture risk assessment tools and subsequent prevention strategies should be modified to accurately identify home care recipients at risk for imminent 1-year fracture.     

Thumbprinting Locally Advanced Pancreatic Cancer: Have We Developed the Optimal Staging System?

Annals of Surgical Oncology -