Executive control of bureaucracy and presidential cabinet appointments in East Asian democracies

This article examines the role of cabinet appointments in controlling the bureaucracy in presidential democracies. I demonstrate how administrative challenges stemming from the structure of the bureaucracy shape presidential choice of ministers. Analyzing a sample of four East Asian cases from 1986 through 2013, I find that presidents are more likely to select ministers from the civil service as bureaucracies are more professionalized, controlling for several political factors. Further evidence from qualitative interviews and case studies suggests that, in professionalized systems equipped with a sizable pool of talent but lacking responsiveness, presidents tend to promote ideologically aligned senior civil servants. However, in politicized systems, where presidents easily obtain responsiveness but face a low level of competence, policy experts tend to be selected from outside the bureaucracy. My findings have important implications for the regulatory governance and state capacity of East Asia, demonstrating the value of balancing between responsiveness and competence

Adenosine A2A receptors in Parkinson’s disease treatment

Latest results on the action of adenosine A2A receptor antagonists indicate their potential therapeutic usefulness in the treatment of Parkinson’s disease. Basal ganglia possess high levels of adenosine A2A receptors, mainly on the external surfaces of neurons located at the indirect tracts between the striatum, globus pallidus, and substantia nigra. Experiments with animal models of Parkinson’s disease indicate that adenosine A2A receptors are strongly involved in the regulation of the central nervous system. Co-localization of adenosine A2A and dopaminergic D2 receptors in striatum creates a milieu for antagonistic interaction between adenosine and dopamine. The experimental data prove that the best improvement of mobility in patients with Parkinson’s disease could be achieved with simultaneous activation of dopaminergic D2 receptors and inhibition of adenosine A2A receptors. In animal models of Parkinson’s disease, the use of selective antagonists of adenosine A2A receptors, such as istradefylline, led to the reversibility of movement dysfunction. These compounds might improve mobility during both monotherapy and co-administration with L-DOPA and dopamine receptor agonists. The use of adenosine A2A receptor antagonists in combination therapy enables the reduction of the L-DOPA doses, as well as a reduction of side effects. In combination therapy, the adenosine A2A receptor antagonists might be used in both moderate and advanced stages of Parkinson’s disease. The long-lasting administration of adenosine A2A receptor antagonists does not decrease the patient response and does not cause side effects typical of L-DOPA therapy. It was demonstrated in various animal models that inhibition of adenosine A2A receptors not only decreases the movement disturbance, but also reveals a neuroprotective activity, which might impede or stop the progression of the disease. Recently, clinical trials were completed on the use of istradefylline (KW-6002), an inhibitor of adenosine A2A receptors, as an anti-Parkinson drug

Cotrel–Dubousset instrumentation in neuromuscular scoliosis

The study design is retrospective. The aim is to describe our experience about the treatment of patients with neuromuscular scoliosis (NMS) using Cotrel–Dubousset instrumentation. Neuromuscular scoliosis are difficult deformities to treat. A careful assessment and an understanding of the primary disease and its prognosis are essential for planning treatment which is aimed at maximizing function. These patients may have pelvic obliquity, dislocation of the hip, limited balance or ability to sit, back pain, and, in some cases, a serious decrease in pulmonary function. Spinal deformity is difficult to control with a brace, and it may progress even after skeletal maturity has been reached. Surgery is the main stay of treatment for selected patients. The goals of surgery are to correct the deformity producing a balanced spine with a level pelvis and a solid spinal fusion to prevent or delay secondary respiratory complications. The instrumented spinal fusion (ISF) with second-generation instrumentation (e.g., Luque–Galveston and unit rod constructs), are until 1990s considered the gold standard surgical technique for neuromuscular scoliosis (NMS). Still in 2008 Tsirikos et al. said that “the Unit rod instrumentation is a common standard technique and the primary instrumentation system for the treatment of pediatric patients with cerebral palsy and neuromuscular scoliosis because it is simple to use, it is considerably less expensive than most other systems, and can achieve good deformity correction with a low loss of correction, as well as a low prevalence of associated complications and a low reoperation rate.” In spite of the Cotrel–Dubousset (CD) surgical technique, used since the beginning of the mid 1980s, being already considered the highest level achieved in correction of scoliosis by a posterior approach, Teli et al., in 2006, said that reports are lacking on the results of third-generation instrumentation for the treatment of NMS. Patients with neuromuscular disease and spinal deformity treated between 1984 and 2008 consecutively by the senior author (G.D.G.) with Cotrel–Dubousset instrumentation and minimum 36 months follow-up were reviewed, evaluating correction of coronal deformity, sagittal balance and pelvic obliquity, and rate of complications. 24 patients (Friedreich’s ataxia, 1; cerebral palsy, 14; muscular dystrophy, 2; polio, 2; syringomyelia, 3; spinal atrophy, 2) were included. According the evidence that the study period is too long (1984–2008) and that in more than 20 years many things changed in surgical strategy and techniques, all patients were divided in two groups: only hooks (8 patients) or hybrid construct (16 patients). Mean age was 18.1 years at surgery (range 11 years 7 months–max 31 years; in 17 cases the age at surgery time was between 10 and 20 years old; in 6 cases it was between 20 and 30 and only in 1 case was over 30 years old). Mean follow-up was 142 months (range 36–279). The most frequent patterns of scoliosis were thoracic (10 cases) and thoracolumbar (9 cases). In 8 cases we had hypokyphosis, in 6 normal kyphosis and in 9 hyperkyphosis. In 8 cases we had a normal lordosis, in 11 a hypolordosis and in 4 a hyperlordosis. In 1 case we had global T4–L4 kyphosis. In 8 cases there were also a thoracolumbar kyphosis (mean value 24°, min 20°–max 35°). The mean fusion area included 13 vertebrae (range 6–19); in 17 cases the upper end vertebra was over T4 and in 11 cases the lower end vertebra was over L4 or L5. In 7 cases the lower end vertebra was S1 to correct the pelvic obliquity. In 5 cases the severity of the deformity (mean Cobb’s angle 84.2°) imposed a preoperative halo traction treatment. There were 5 anteroposterior and 19 posterior-only procedures. In 10 cases, with low bone quality, the arthrodesis was performed using iliac grafting technique while in the other (14 cases) using autologous bone graft obtained in situ from vertebral arches and spinous processes (in all 7 cases with fusion extended until S1, it was augmented with calcium phosphate). The mean correction of coronal deformity and pelvic obliquity averaged, respectively, 57.2% (min 31.8%; max 84.8%) and 58.9% (mean value preoperative, 18.43°; mean value postoperative, 7.57°; mean value at last follow-up, 7.57°). The sagittal balance was always restored, reducing hypo or hyperkyphosis and hypo or hyperlordosis. Also in presence of a global kyphosis, we observed a very good restoration (preoperatory, 65°; postoperatory, 18° kyphosis and 30° lordosis, unmodified at last f.u.). The thoracolumbar kyphosis, when present (33.3% of our group) was always corrected to physiological values (mean 2°, min 0°–max 5°). The mean intraoperative blood lost were 2,100 cc (min 1,400, max 5,350). Major complications affected 8.3% of patients, and included 1 postoperative death and 1 deep infection. Minor complications affected none of patients. CD technique provides lasting correction of spinal deformity in patients with neuromuscular scoliosis, with a lower complications rate compared to reports on second-generation instrumented spinal fusion

A 2a adenosine receptor: Structures, modeling, and medicinal chemistry

Many selective agonists and antagonists of the A 2A adenosine receptor (AR) have been reported, while allosteric modulators specific for this receptor are still needed. Many heterocyclic chemotypes have been discovered as A 2A AR antagonists, while most of the known AR agonists are nucleosides or 3,5-dicyanopyridine derivatives. A few A 2A AR ligands have been in clinical trials as antihypertensives, anti-inflammatory or diagnostic compounds (agonists), and as drugs for treating Parkinson’s disease and cancer (antagonists). The A 2A AR has become one of the most widely investigated G protein-coupled receptor (GPCR) structures using X-ray crystallography and also biophysical techniques such as NMR. Thus, the design of agonists, antagonists, and allosteric modulators has become structure-based, with numerous examples of in silico approaches, including virtual ligand screening (VLS), leading to the discovery of both novel agonists and antagonists