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A B S T R AC TBackground: Melatonin may reduce REM-sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. Objective: To assess the efficacy of prolonged-release (PR) melatonin for RBD in PD. Methods: Randomized, double-blind, placebocontrolled, parallel-group trial with an 8-week intervention and 4-week observation pre-and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged-release melatonin (Circadin) or matched placebo, ingested orally once-daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed-model analysis of variance (n = 15 per group). Results: No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = −3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). Conclusion: Prolonged-release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD.

Background Two-level cervical degenerative disc disease (cDDD) can be effectively treated by anterior cervical discectomy and fusion (ACDF) similarly to single-level cDDD. Traditionally an anterior plate construct (APC) approach has been utilized, but ACDF without plate with a locking stand-alone cage (LSC) approach has emerged as an alternative option. The aim of this study was to compare the clinical outcome of LSC and APC in contiguous two-level ACDF used to treat cDDD the current literature. Methods Searches of seven electronic databases from inception to March 2018 were conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Extracted data were analysed using meta-analysis of proportions. ResultsThe nine observational studies that satisfied all criteria described a pooled cohort of 687 contiguous two-level cDDD cases managed by ACDF, with 302 (44%) and 385 (56%) managed by LSC and APC approaches, respectively. When compared with APC, LSC was associated with significantly increased subsidence likelihood (OR 2.75; p < 0.001), greater disc height (MD 0.60 mm; p = 0.04) and reduced cervical lordosis (MD − 2.52°; p = 0.04) at last follow-up. Operative outcomes, fusion rates, functional scores and postoperative dysphagia rates were comparable. Conclusion Although significant radiological differences were most evident, the comparability between LSC and APC in contiguous two-level ACDF with respect to all other clinical outcomes does not implicate one approach as clearly superior to the other in two-level ACDF. Larger, randomized studies with longer follow-up are required to delineate outcomes further to validate the findings of this study.

BackgroundThe initiation of hepatitis B virus (HBV) replication involves the formation of covalently closed circular DNA (cccDNA) and its transcription into pregenomic RNA (pgRNA) in hepatocyte nuclei. The regulatory mechanism of HBV replication by acetyltransferase is thus far not well understood, but human acetyltransferase has been reported as being involved in the regulation of HBV replication.ResultsDepletion of KAT8 or HAT1 via RNA interference (RNAi) markedly down-regulated HBV-DNA and pgRNA levels in HepG2.2.15 cells, with KAT8 knockdown reducing both HBsAg and HBeAg more than HAT1 knockdown. Consistent with these observations, HBV replication regulators hepatocyte nuclear factor-4-α (HNF4α) and peroxisome proliferator-activated receptor gamma coactivator- (PPARGC-) 1-α were decreased following knockdown of HAT1 or KAT8.ConclusionsThese data suggest that KAT8 or HAT1 regulate HBV replication and may be potential drug targets of anti-HBV therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-015-0059-1) contains supplementary material, which is available to authorized users.