• Gillespie Munck posted an update 13 hours, 18 minutes ago

    N6-Methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on the N6 nitrogen of adenosine. However, the roles of m6A in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate the function and mechanism of methyltransferase-like 3 (METTL3) in OSCC tumorigenesis. Clinically, METTL3 was significantly upregulated in tissue samples and correlated with the poor prognosis of OSCC patients. Functionally, loss and gain studies illustrated that METTL3 promoted the proliferation, invasion, and migration of OSCC cells in vitro, and METTL3 knockdown inhibited tumor growth in vivo. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that METTL3 targeted the 3′ UTR (near to stop codon) of the c-Myc transcript to install the m6A modification, thereby enhancing its stability. Furthermore, results revealed that YTH N6-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m6A-increased stability of c-Myc mRNA catalyzed by METTL3. In conclusion, our findings herein identify that METTL3 accelerates the c-Myc stability via YTHDF1-mediated m6A modification, thereby giving rise to OSCC tumorigenesis. Aneurysms in the sinuses of Valsalva (SVA) are the least frequent and occur due to a weakness in the aortic wall that forms part of the sinus. This causes dilatation and the formation of a blind pocket in one of the aortic sinuses (usually he right sinus and less frequently the posterior one). It may be congenital or acquired in a congenital SVA, the condition is frequently associated with Marfan’s syndrome or other connective tissue disorders; instead, acquired forms of sinus of Valsalva aneurysm are associated with infections (syphilis, bacterial endocarditis, and tuberculosis), atherosclerosis and medial cystic necrosis, traumatic and degenerative diseases, abuse of drugs or alcoholism. Despite SVA is a well-known anomaly, autopsy images or reviews of the condition are very uncommon. Indeed we report here a fatal case of SVA in a 58-year-old homeless man found dead on the street. The autopsy, performed to determine the cause of death, releaved a massive aneurysm (in excess of 4 cm) involving the right coronary sinus of the aorta. In this case, the aneurysm may be an accidental finding in effect we found no tromboses inside the aneurysm and the ostium was not obstructed, therefore the cause of death could be attribuited to fatal arrhythmia. AIM The aim of this study was to determine the efficacy and safety of cranial electrotherapy stimulation (CES) as an add-on treatment for TD. METHODS A randomized, double-blind, sham-controlled trial was conducted at an outpatient, single-center academic setting. selleck screening library A total of 62 patients aged 6-17 years with TD and lack of clinical response to 4 weeks’ pharmacotherapy were enrolled. Patients were divided randomly into 2 groups and given 4 weeks’ treatment, including 30 min sessions of active CES (500 μA-2 mA) or sham CES (lower than 100 μA) per day for 40 d on weekdays. Change in Yale Global Tic Severity Scale (YGTSS), Clinical Global Impression-severity of illness-severity (CGI-S) and Hamilton Anxiety Scale-14 items (HAMA-14) were performed at baseline, week 2, week 4. Adverse events (AEs) were also evaluated. RESULTS 53 patients (34 males and 9 females) completed the trial, including 29 in the active CES group and 24 in the sham CES group. Both groups showed clinical improvement in tic severities compared to baseline respectively at week 4. Participants receiving active CES showed a reduction of 31.66 % in YGTSS score, compared with 23.96 % in participants in sham CES group, resulting in no significant difference between the two groups (t = 1.54, p = 0.13). CONCLUSION Four-week’s treatment of CES for children and adolescents with TD is effective and safe, but the improvement for tic severity may be related to placebo effect. BACKGROUND Cervical myelopathy is a common and debilitating chronic spinal cord dysfunction. Treatment includes anterior and/or posterior surgical intervention to decompress the spinal cord and stabilize the spine, but no consensus has been made as to the preferable surgical intervention. The objective of this study was to develop an finite element model of the healthy and myelopathic C2-T1 cervical spine and common anterior and posterior decompression techniques to determine how spinal cord stress and strain is altered in healthy and diseased states. METHODS A finite element model of the C2-T1 cervical spine, spinal cord, pia, dura, cerebral spinal fluid, and neural ligaments was developed and validated against in vivo human displacement data. To model cervical myelopathy, disc herniation and osteophytes were created at the C4-C6 levels. Three common surgical interventions were then incorporated at these levels. FINDINGS The finite element model accurately predicted healthy and myelopathic spinal cord displacement compared to motions observed in vivo. Spinal cord strain increased during extension in the cervical myelopathy finite element model. All surgical techniques affected spinal cord stress and strain. Specifically, adjacent levels had increased stress and strain, especially in the anterior cervical discectomy and fusion case. INTERPRETATIONS This model is the first biomechanically validated, finite element model of the healthy and myelopathic C2-T1 cervical spine and spinal cord which predicts spinal cord displacement, stress, and strain during physiologic motion. Our findings show surgical intervention can cause increased strain in the adjacent levels of the spinal cord which is particularly worse following anterior cervical discectomy and fusion. BACKGROUND Adolescent idiopathic scoliosis is a common condition affecting 2.5% of the general population. Vertebral body stapling was introduced as a method of fusionless growth modulation for the correction of moderate idiopathic scoliosis (Cobb angles of 20-40°), and was claimed to be more effective than bracing and less invasive than fusion. The aim of this study was to assess the effect of vertebral body stapling on the stiffness of a thoracic motion segment unit under moment controlled load, and to assess the vertebral structural damage caused by the staples. METHODS Thoracic spine motion segments from 6 to 8 week old calves (n=14) were tested in flexion/extension, lateral bending, and axial rotation. The segments were tested un-instrumented, then a left anterolateral intervertebral Shape Memory Alloy (SMA) staple was inserted and the test was repeated. Data were collected from the tenth load cycle of each sequence and stiffness was calculated. The staples were carefully removed and the segments were studied with micro-computed tomography to assess physical damage to the bony structure.