Citations

This article is linked to Tye‐Din and Fang et al papers. To view these articles visit https://doi.org/10.1111/apt.14287 and https://doi.org/10.1111/apt.14250.

ABSTRACTBackgroundA number of genetic loci are associated with risk for Parkinson's disease (PD) based on genome‐wide association studies; however, the relationship between genetic variants and nigrostriatal degeneration, which is the structural correlate of parkinsonism, has not been reported.ObjectivesWe quantified nigrostriatal dopaminergic integrity with image analysis of putaminal tyrosine hydroxylase immunoreactivity in 492 brains with Lewy body disease and used this pathologic endophenotype to explore possible association with PD genetic variants.MethodsThe study cases had Lewy‐related pathology and variable degrees of nigrostriatal degeneration. They were assigned to one of the following clinical subgroups according to their predominant clinical syndrome: parkinsonism‐predominant, parkinsonism+dementia, and dementia‐predominant. In addition to putaminal tyrosine hydroxylase immunoreactivity, semiquantitative scoring was used to assess substantia nigra neuronal loss. A total of 29 PD genetic risk variants were genotyped on each case.ResultsWhen compared with controls, tyrosine hydroxylase immunoreactivity was reduced in Lewy body cases in the dorsolateral (79%) and ventromedial (57%) putamen. The dorsolateral region was better preserved in dementia‐predominant cases than in cases with parkinsonism. Dorsolateral putaminal tyrosine hydroxylase immunoreactivity correlated with neuronal loss in the ventrolateral substantia nigra. Genetic analyses showed no significant association of PD risk variants with putaminal tyrosine hydroxylase immunoreactivity.ConclusionsThe results confirm regional differences in putaminal dopaminergic degeneration and vulnerability of nigrostriatal pathway in Lewy body disorders with parkinsonism. The lack of association with PD genetic risk variants suggests that they may not be associated with quantitative endophenotypes of nigrostriatal degeneration, but more likely related to the risk of disease per se. © 2017 International Parkinson and Movement Disorder Society

Abstract Isolated cartilage defects can lead to significant pain and disability, prompting the development of a number of options for restorative treatment. Each method has advantages and limitations, and no single technique has gained widespread use. We present a technique for implantation of a cryopreserved osteochondral allograft (Cartiform) for the treatment of full‐thickness cartilage defects. Cartiform is a cryopreserved osteochondral allograft composed of chondrocytes, chondrogenic growth factors, and extracellular matrix proteins. This implant allows for regenerative treatment of full‐thickness cartilage lesions in a single surgical procedure. Technique Video video See video under supplementary data.

Bone atrophy and its related fragility fractures are frequent, late side effects of radiotherapy in cancer survivors and have a detrimental impact on their quality of life. In another study, we showed that parathyroid hormone 1‐34 and anti‐sclerostin antibody attenuates radiation‐induced bone damage by accelerating DNA repair in osteoblasts. DNA damage responses are partially regulated by the ubiquitin proteasome pathway. In the current study, we examined whether proteasome inhibitors have similar bone‐protective effects against radiation damage. MG132 treatment greatly reduced radiation‐induced apoptosis in cultured osteoblastic cells. This survival effect was owing to accelerated DNA repair as revealed by γH2AX foci and comet assays and to the up‐regulation of Ku70 and DNA‐dependent protein kinase, catalytic subunit, essential DNA repair proteins in the nonhomologous end‐ joining pathway. Administration of bortezomib (Bzb) reversed the loss of trabecular bone structure and strength in mice at 4 wk after focal radiation. Histomorphometry revealed that Bzb significantly increased the number of osteoblasts and activity in the irradiated area and suppressed the number and activity of osteoclasts, regardless of irradiation. Two weeks of Bzb treatment accelerated DNA repair in bone‐lining osteoblasts and thus promoted their survival. Meanwhile, it also inhibited bone marrow adiposity. Taken together, we demonstrate a novel role of proteasome inhibitors in treating radiation‐induced osteoporosis.—Chandra, A., Wang, L., Young, T., Zhong, L., Tseng, W.‐J., Levine, M. A., Cengel, K., Liu, X. S., Zhang, Y., Pignolo, R. J., Qin, L. Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation‐induced osteoporosis. FASEB J. 32, 52‐62 (2018). www.fasebj.org

Abstract Horizontal cleavage meniscus tears are a common orthopedic injury often treated with partial or total meniscectomy versus repair. This Technical Note presents a technique for all‐inside repair with uniform compression of the superior and inferior leaflets by placement of multiple circumferential compression stitches using an all‐inside self‐retrieving suture passing device. The currently described technique provides several advantages for all‐inside repair of a horizontal cleavage tear: (1) eliminates the need for a posterior incision, (2) minimizes the risk of neurovascular injury, (3) uses standard arthroscopy portals (or small modifications), and (4) requires only a single suture deployment with a self‐retrieving device for each circumferential compression stitch. The resulting circumferential stitch provides uniform compression to the superior and inferior leaflets, promoting meniscal healing. This configuration has been shown to have the highest load to failure of all repair patterns. Technique Video video See video under supplementary data.