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Although the administration of dopamine precursor levodopa remains as the mainstay for the treatment of Parkinson's disease, long-term exposure to levodopa often causes a disabling complication, referred to as levodopa-induced dyskinesias. Therefore, the development of new therapeutic interventions to dampen levodopa-induced dyskinesias and parkinsonian motor deficits is needed in the treatment of Parkinson's disease. Intracerebral brain infusion has the merit of being able to specifically deliver any drug into any brain part. By using an intracerebral infusion system equipped with implantable, programmable, and refillable pumps, we show herein that continuous intrastriatal administration of memantine (MMT), which is a non-competitive N-methyl-D-aspartate receptor antagonist, attenuates levodopa-induced dyskinesias and parkinsonian signs in 6-hydroxydopamine-lesioned hemiparkinsonian mice that received daily levodopa treatment. Corroborating the general thought that overactivation of the striatal N-methyl-D-aspartate receptor function might generate levodopa-induced dyskinesias and parkinsonism, our results suggest that a continuous intrastriatal MMT infusion can be beneficial for the management of Parkinson's disease with levodopa-induced dyskinesias. Our study also provides indications for the prototypic use of pharmacological deep-brain modulation through intracerebral infusion systems for treating medically intractable movement disorders.

Parkinson’s disease (PD) is caused by a progressive degeneration of nigral dopaminergic cells leading to striatal dopamine deficiency. From the perspective of antiparkinsonian drug mechanisms, pharmacologic treatment of PD can be divided into symptomatic and disease-modifying (neuroprotective) therapies. An increase in the level and activity of the Abelson non-receptor tyrosine kinase (c-Abl) has been identified in both human and mouse brains under PD conditions. In the last decade, it has been observed that the inhibition of c-Abl activity holds promise for protection against the degeneration of nigral dopaminergic cells in PD and thereby exerts antiparkinsonian effects. Accordingly, c-Abl inhibitors have been applied clinically as a disease-modifying therapeutic strategy for PD treatment. Moreover, in a series of studies, including that presented here, experimental evidence suggests that in a mouse model of parkinsonism induced by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, c-Abl inhibition exerts an immediate effect improving motor impairments by normalizing altered activity in striatal postsynaptic signaling pathways mediated by Cdk5 (cyclin-dependent kinase 5) and DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein 32 kDa). Based on this, we suggest that c-Abl inhibitors represent an ideal antiparkinsonian agent that has both disease-modifying and symptomatic effects. Future research is required to carefully evaluate the therapeutic efficacy and clinical challenges associated with applying c-Abl inhibitors to the treatment of PD.

Osteosarcoma is the most common malignant primary bone tumor that occurs most frequently in the second decade of life but rarely in patients over 40 years of age. The most common primary sites of osteosarcoma are the distal femur followed by proximal tibia and proximal humerus, and involvement of the wrist is extremely rare. Moreover, dedifferentiated osteosarcoma is also a rare condition that progresses to high-grade osteosarcoma from low-grade osteosarcoma, usually central low-grade osteosarcoma or parosteal osteosarcoma that bears MDM2 and/or CDK4 gene amplifications. We herein report an extremely rare case of dedifferentiated osteosarcoma arising in the distal ulna of an adult over 40 years of age. The patient was a 46-year-old man with a 2-month history of pain in his left swollen wrist. The initial radiological findings suggested a benign bone tumor in the distal ulna, and the lesion was marginally excised at the nearby hospital. Although the pathological diagnosis at the nearby hospital suggested a benign cartilaginous tumor, the tumor recurred in an aggressive manner 8 months after the initial surgery. The patient was referred to our hospital, and an incisional biopsy showed a high-grade osteosarcoma. The primary tumor was retrospectively re-evaluated at our hospital and diagnosed as low-grade osteosarcoma. Since neoadjuvant chemotherapy failed to shrink the tumor, the patient had to undergo below the elbow amputation to cure the disease. Although the tumor was negative for MDM2 nor CDK4, the definitive diagnosis of dedifferentiated osteosarcoma was made according to the clinical course and the histological findings. Lung metastases were found 10 months after the amputation, which were successfully treated by neoadjuvant chemotherapy and surgery. The patient has been doing well with no evidence of disease for 1 year and 6 months. Surprisingly, the literature review revealed that many low-grade osteosarcomas of the distal ulna progressed to high-grade dedifferentiated osteosarcomas. One should bear in mind that the diagnosis and treatment for bone-forming tumors of the distal ulna should be made very carefully because, although rare, it is possible that the tumor may initially appear as a benign or low-grade malignant tumor and may progress to high-grade osteosarcoma.

Background: Humeral head inferior subluxation often occurs immediately after osteosynthesis for proximal humeral fracture; however, the underlying cause remains largely unknown. In addition, the prognosis of postoperative inferior subluxation has not been fully investigated. This study aimed to clarify the predictive factors that affected the onset of postoperative inferior subluxation using multivariate analysis and examine the postoperative course of inferior subluxation and its influence on postoperative outcomes. Methods: We retrospectively reviewed 212 patients who underwent osteosynthesis for Neer 2- or 3-part proximal humeral fractures. In the multivariate analysis, the dependent variable was set as the inferior subluxation observed 1 week after the surgery. The explanatory variables included age, sex, affected side, body mass index, smoking, local osteoporosis, preoperative axillary nerve injury, time from injury to surgery, fracture dislocation, fracture pattern, preoperative inferior subluxation, surgical procedure, surgical approaches, blood loss, operative time, and postoperative drainage. Baseline variables, which were observed to be significant in the univariate analysis, were included in multivariate models. Furthermore, based on the presence of inferior subluxation at 1 week after the surgery, we divided the patients into two groups: with inferior subluxation (+IS group) and without inferior subluxation (−IS group). We compared the postoperative outcomes (incidence of postoperative complications and range of motion) between these two groups. Results: Of 212 patients, 64 (30.7%) experienced inferior subluxation at 1 week after the surgery. On multivariate analyses, preoperative inferior subluxation (odds ratio = 4.69; 95% confidence interval = 2.45-9.76; P

Investigations into infrared radiation transmission of periodic subwavelength Pd hole arrays reveal a transmittance attenuation of the main resonant peak upon exposure to hydrogen of the hole arrays. The attenuation is attributed to the formation of Pd hydride, which results in the combine effects of lattice expansion of the Pd film, generating a decrease in the hole width, and optical properties variations of the Pd film, giving rise to stronger damping of the surface plasmons. The reduction in the hole width of the arrays is estimated to be of the order of a few tens of nanometers. Our results illustrate the possibility of detecting minute changes in the structure of the metallic hole arrays by monitoring the transmittance of the resonant peaks. The all-optical hydrogen sensing scheme presented in this work is thought to find applications in the detection of hydrogen at concentration levels near the lower flammability threshold for alarm purposes. [ABSTRACT FROM AUTHOR]