Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered. Echocardiography was performed to evaluate cardiac function 1 week after surgery. The gene and protein expression levels in the left ventricles (LVs) were determined with real-time PCR, western blotting, and immunofluorescence. Moreover, immune cell infiltration into the LVs was analyzed by flow cytometry. Survival rate and reduced LV function were significantly improved by the treatment with SR9009 after MI. The expression level and plasma concentration of brain natriuretic peptide were significantly lower in MI mice treated with SR9009 (MI+SR) than in MI mice treated with vehicle (MI+V). Moreover, the mRNA expression levels of inflammatory-related molecules such as Il6, Mcp1, Ly6g, Cd11b, matrix metallopeptidase (Mmp)9, and the protein expression levels of phosphorylated NF-κB p65, phosphorylated ERK, and phosphorylated p38 were also significantly lower in MI+SR than in MI+V. Immunofluorescence intensity for MMP-9 was enhanced in the LVs, but was less so in MI+SR than in MI+V. Furthermore, infiltrations of neutrophils and proinflammatory macrophages in the LVs were dramatically increased in MI+V and were significantly suppressed in MI+SR. Rev-erb agonist SR9009 treatment inhibited post-MI mortality and improved cardiac function through modulating inflammation and remodeling process.

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Anterior reduction and interbody fusion fixation has not been compared directly with posterior reduction and short-segmental pedicle screw fixation for lower cervical dislocation, and so consensus is lacking as to which is the optimal method. The purpose of this paper is to compare long-term outcomes of the anterior versus posterior approach for traumatic cervical dislocation with spinal cord injury. One hundred and fifty-nine patients could be followed for more than 10 years (follow-up rate 84.1%). Ninety-two patients underwent anterior reduction and interbody fusion and fixation, and 67 patients underwent posterior reduction and short-segmental pedicle screw fixation. Japanese Orthopaedic Association (JOA) scores, the Neck Disability Index (NDI), the American Spinal Injury Association grading (ASIA), Odom's criteria, cervical kyphosis, operative parameters, and surgical or post-operative complications were evaluated. Patients were followed for 10 to 17 years. There was no significant difference in main JOA scores, NDI scores or ASIA scores between the two groups at follow-up. The posterior approach was associated with greater loss of alignment by two years (P = 0.012) and at final follow-up (P < 0.001). The posterior approach group had more blood loss (P < 0.001), longer operation times (P < 0.001), longer hospital stays (P < 0.001) and fewer complications than the anterior approach group. the anterior approach is better than the posterior approach for preserving cervical lordosis, which is associated with a better long-term effect. Lower cervical dislocation with locked facets is common in acute cervical injury. This often leads to the abnormal alignment of the cervical spine, cervical instability and significant functional disability 1-3. Such injury often requires early surgical treatment, with the goal of decompression and reduction. The surgical approaches for lower cervical fracture-dislocation are highly variable and include anterior, posterior, and combined anterior and posterior approaches 4-11. The anterior approach surgery is the most commonly used method, perhaps because it is relatively simple, is familiar to surgeons, and has achieved good results 4,5,11. More importantly, anterior decompression is necessary for patients with disc herniation. However, in some cases, anterior reduction is difficult and also requires posterior reduction 4,12-15. Reduction is easier to achieve with the posterior approach and can provide more stable fixation 7,8,16 , but whether it has a better outcome over a long period of time is unknown. Combined anterior and posterior approaches can not only adequately decompress, but also provide better stability 9. However, the combined approach increases surgical trauma and complexity. Changes in position during surgery also increase the risk of nerve injury 17. Therefore, anterior alone and posterior alone approaches are more common. Kwon compared anterior cervical plate fixation with posterior lateral mass screw-plate and/or interspinous wire fixation for unilateral facet inj...

Insomnia is one of the most common sleep problems with an estimated prevalence of 10% to 15% in the general population. Although adenosine A2A receptor (A2AR) agonists strongly induce sleep, their cardiovascular effects preclude their use in treating sleep disorders. Enhancing endogenous A2AR signaling, however, may be an alternative strategy for treating insomnia, because adenosine levels in the brain accumulate during wakefulness. In the present study, we found that 3,4-difluoro-2-((2-fluoro-4iodophenyl)amino)benzoic acid, denoted A2AR positive allosteric modulator (PAM)-1, enhanced adenosine signaling at the A2AR and induced slow wave sleep (SWS) without affecting body temperature in wild-type male mice after intraperitoneal administration, whereas the SWS-inducing effect of this benzoic acid derivative was abolished in A2AR KO mice. In contrast to the A2AR agonist CGS 21680, the A2AR PAM-1 did not affect blood pressure or heart rate. These findings indicate that enhancing A2AR signaling promotes SWS without cardiovascular effects. Therefore, small molecules that allosterically modulate A2ARs could help people with insomnia to fall asleep.

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