There is growing recognition of cerebrovascular contributions to neurodegenerative diseases. In the walls of cerebral arteries, amyloid-beta (Aβ) accumulation is evident in a majority of aged people and patients with cerebral amyloid angiopathy. Here, we leverage human pluripotent stem cells to generate vascular smooth muscle cells (SMCs) from neural crest progenitors, recapitulating brain-vasculature-specific attributes of Aβ metabolism. We confirm that the lipoprotein receptor, LRP1, functions in our neural-crest-derived SMCs to mediate Aβ uptake and intracellular lysosomal degradation. Hypoxia significantly compromises the contribution of SMCs to Aβ clearance by suppressing LRP1 expression. This enabled us to develop an assay of Aβ uptake by using the neural crest-derived SMCs with hypoxia as a stress paradigm. We then tested several vascular protective compounds in a high-throughput format, demonstrating the value of stem-cell-based phenotypic screening for novel therapeutics and drug repurposing, aimed at alleviating amyloid burden.
Purpose: The study aimed to investigate the utility of ultrasonographic (US) findings in predicting the subsequent radiographic parameters of developmental dysplasia of the hips. Methods: In this 12-year retrospective cohort study, all newborn infants with a positive clinical examination or risk factors were included. They were scheduled for hip ultrasonography in the first 3 months, and subsequent radiographs at 1 year of life. The US images were evaluated using the Graf classification, Harcke's dynamic screening method, and Terjesen's femoral head coverage method. The radiographic images were evaluated using the acetabular index and femoral head position. The overall US or radiographic findings were considered abnormal if they were classified as abnormal for any of their respective parameters. The overall US and radiographic parameters were correlated. Results: A total of 160 patients were included. The overall US and radiographic parameters showed no statistically significant difference (P=0.050). The sensitivity, specificity, and accuracy of the overall US parameters were 57.1%, 84.9%, and 81.3%, respectively. All three individual US parameters showed no statistically significant differences, with the overall radiographic findings and acetabular index (P>0.05). However, they showed a statistically significant difference, with the position of the femoral head (P<0.001), with the US parameters having an excellent negative predictive value of 100% for identifying an abnormal femoral head position. Conclusion: The current study suggests that US findings evaluated in the first 3 months of life showed no statistically significant difference with radiographic findings evaluated at 1 year of life. The US parameters showed an excellent negative predictive value for abnormal femoral head position on radiographs.
Dear Editor,Stress fractures are caused by repeated micro trauma to the bone over a period of time. It can happen in normal bone exposed to abnormal repetitive stress or in abnormal bone receiving normal stress. In healthy individuals, tibia stress fractures occur most frequently amongst athletes who participate in activities that involve prolonged walking, running or jumping. 1 The tibia shaft is most commonly affected, whereas the proximal tibia is less common. 2 Risk factors include excessive training, alteration in normal gait biomechanics such as tightness of calf muscles, unequal leg length, osteoporotic bone and vitamin D deficiency. 3,4 This type of fracture can be easily misdiagnosed due to its clinical presentation and location near the knee, 5,6 which can mimic medial-sided osteoarthritis, meniscal injuries and pes anserinus bursitis. We describe an atypical presentation of atraumatic proximal tibia stress fracture in a young healthy male with no known risk factors.
Background: Unstable distal clavicles experience high non-union rates, prompting surgeons to recommend surgery for more predictable outcomes. There is a lack of consensus on the optimal method of surgical fixation, with an array of techniques described in the literature. We describe an alternative method of fixation involving the use of a distal clavicular anatomical locking plate with Fibertape cerclage augmentation in our series of patients. Methods: Nine patients (8 males and 1 female), with a mean age of 36 years, who sustained unstable fracture of the distal clavicle in our institution were treated with our described technique. Postoperative range of motion, functional and pain scores, and time to radiographic union were measured over a mean follow-up period of 10 months. Incidences of postoperative complications were also recorded. Results: At the last patient consult, the mean visual analog scale score was 0.88±0.35, with a mean Disability of the Arm, Shoulder, and Hand (DASH) score of 1.46±0.87 and American Shoulder and Elbow Surgeons (ASES) score of 94.1±3.57. The mean range of motion achieved was forward flexion at 173°±10.6°, abduction at 173°±10.6°, and external rotation at 74.4°±10.5°. All patients achieved internal rotation at a vertebral height of at least L2 with radiographical union at a mean of 10 weeks. No removal of implants was required. Conclusions: Our described technique of augmented fixation of the distal clavicle is effective, produces good clinical outcomes, and has minimal complications.
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