ABSTRACT
BACKGROUND: 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, placebo-controlled, 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. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Subject(s)
Eye Movements/drug effects , Melatonin/therapeutic use , Parkinson Disease/drug therapy , REM Sleep Behavior Disorder/drug therapy , Aged , Clonazepam/therapeutic use , Double-Blind Method , Fatigue/drug therapy , Female , Humans , Male , Melatonin/metabolism , Middle Aged , Polysomnography/methods , REM Sleep Behavior Disorder/diagnosisABSTRACT
Spinal fusion via anterior lumbar interbody fusion (ALIF) can offer symptomatic relief to patients that suffer severe low back pain, radiculopathy, and claudication. However, a detailed working knowledge of the thoracic, abdominal, and lumbar anatomy, particularly of the vasculature, is vital. We report the case of a 68-year-old man who presented with radiculopathy and progressively worsening low back pain despite 9 months of unsuccessful conservative therapy and pain management. Preoperative computed tomography and magnetic resonance imaging revealed a rare anatomical variation, with an anomalous left-sided inferior vena cava and anomalous aorta. The patient was surgically treated with ALIF at L4,5 and L5 S1 via an altered surgical window. Given the anomalous anatomy of the patient, instead of performing the procedure after mobilizing both of the transposed abdominal great vessels, the inferior vena cava and the abdominal aorta, the ALIF was uneventfully performed in the window between these vessels. There were no perioperative or postoperative complications. At 12-week postoperative follow-up, X-ray imaging demonstrated successful implantation of ALIF cages with no recurrence of symptoms. A detailed working knowledge of anatomy is important, particularly if anatomical variations are present. This has implications for preoperative surgical planning, which is integral to the safety and the success of procedures.
Subject(s)
Aorta, Thoracic/abnormalities , Low Back Pain/surgery , Spinal Fusion/methods , Vena Cava, Inferior/abnormalities , Aged , Aorta, Thoracic/diagnostic imaging , Humans , Low Back Pain/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Magnetic Resonance Imaging , Male , Radiculopathy/diagnostic imaging , Radiculopathy/surgery , Tomography, X-Ray Computed , Vena Cava, Inferior/diagnostic imagingABSTRACT
BACKGROUND: The 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. RESULTS: Depletion 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. CONCLUSIONS: These data suggest that KAT8 or HAT1 regulate HBV replication and may be potential drug targets of anti-HBV therapy.