Identification of ortho catechol-containing isoflavone as a privileged scaffold that directly prevents the aggregation of both amyloid ß plaques and tau-mediated neurofibrillary tangles and its in vivo evaluation.

In this study, polyhydroxyisoflavones that directly prevent the aggregation of both amyloid ß (Aß) and tau were expediently synthesized via divergent Pd(0)-catalyzed Suzuki-Miyaura coupling and then biologically evaluated. By preliminary structure-activity relationship studies using thioflavin T (ThT) assays, an ortho-catechol containing isoflavone scaffold was proven to be crucial for preventing both Aß aggregation and tau-mediated neurofibrillary tangle formation. Additional TEM experiment confirmed that ortho-catechol containing isoflavone 4d significantly prevented the aggregation of both Aß and tau. To investigate the mode of action (MOA) of 4d, which possesses an ortho-catechol moiety, 1H-15N HSQC NMR analysis was thoroughly performed and the result indicated that 4d could directly inhibit both the formation of Aß42 fibrils and the formation of tau-derived neurofibrils, probably through the catechol-mediated nucleation of tau. Finally, 4d was demonstrated to alleviate cognitive impairment and pathologies related to Alzheimer's disease in a 5XFAD transgenic mouse model.

Validity of Quantitative Lymphoscintigraphy as a Lymphedema Assessment Tool for Patients With Breast Cancer.

OBJECTIVE: To evaluate the validity of quantitative lymphoscintigraphy as a useful lymphedema assessment tool for patients with breast cancer surgery including axillary lymph node dissection (ALND). METHODS: We recruited 72 patients with lymphedema after breast cancer surgery that included ALND. Circumferences in their upper limbs were measured in five areas: 15 cm proximal to the lateral epicondyle (LE), the elbow, 10 cm distal to the LE, the wrist, and the metacarpophalangeal joint. Then, maximal circumference difference (MCD) was calculated by subtracting the unaffected side from the affected side. Quantitative asymmetry indices (QAI) were defined as the radiopharmaceutical uptake ratios of the affected side to the unaffected side. Patients were divided into 3 groups by qualitative lymphoscintigraphic patterns: normal, decreased function, and obstruction. RESULTS: The MCD was highest in the qualitative obstruction (2.76±2.48) pattern with significant differences from the normal (0.69±0.78) and decreased function (1.65±1.17) patterns. The QAIs of the axillary LNs showed significant differences among the normal (0.82±0.29), decreased function (0.42±0.41), and obstruction (0.18±0.16) patterns. As the QAI of the axillary LN increased, the MCD decreased. The QAIs of the upper limbs were significantly higher in the obstruction (3.12±3.07) pattern compared with the normal (1.15±0.10) and decreased function (0.79±0.30) patterns. CONCLUSION: Quantitative lymphoscintigraphic analysis is well correlated with both commonly used qualitative lymphoscintigraphic analysis and circumference differences in the upper limbs of patients with breast cancer surgery with ALND. Quantitative lymphoscintigraphy may be a good alternative assessment tool for diagnosing lymphedema after breast cancer surgery with ALND.

Change of Brain Functional Connectivity in Patients With Spinal Cord Injury: Graph Theory Based Approach.

OBJECTIVE: To investigate the global functional reorganization of the brain following spinal cord injury with graph theory based approach by creating whole brain functional connectivity networks from resting state-functional magnetic resonance imaging (rs-fMRI), characterizing the reorganization of these networks using graph theoretical metrics and to compare these metrics between patients with spinal cord injury (SCI) and age-matched controls. METHODS: Twenty patients with incomplete cervical SCI (14 males, 6 females; age, 55±14.1 years) and 20 healthy subjects (10 males, 10 females; age, 52.9±13.6 years) participated in this study. To analyze the characteristics of the whole brain network constructed with functional connectivity using rs-fMRI, graph theoretical measures were calculated including clustering coefficient, characteristic path length, global efficiency and small-worldness. RESULTS: Clustering coefficient, global efficiency and small-worldness did not show any difference between controls and SCIs in all density ranges. The normalized characteristic path length to random network was higher in SCI patients than in controls and reached statistical significance at 12%-13% of density (p<0.05, uncorrected). CONCLUSION: The graph theoretical approach in brain functional connectivity might be helpful to reveal the information processing after SCI. These findings imply that patients with SCI can build on preserved competent brain control. Further analyses, such as topological rearrangement and hub region identification, will be needed for better understanding of neuroplasticity in patients with SCI.

Effect of dominant hand paralysis on quality of life in patients with subacute stroke.

OBJECTIVE: To evaluate the degree to which the paralysis of a dominant hand affects quality of life (QOL) in patients with subacute stroke. METHODS: We recruited 75 patients with subacute hemiplegic stroke. Patients were divided into two groups according to the location of the lesion and the side of the dominant hand. Group 1 consisted of patients whose strokes affected the dominant hand (i.e., right hemiplegia and right dominant hand or left hemiplegia and left dominant hand). Group 2 consisted of patients whose strokes affected the non-dominant hand (i.e., left hemiplegia and right dominant hand or right hemiplegia and left dominant hand). The primary outcome measure was the Short-Form 36-Item Health Survey (SF-36), which was used to evaluate health-related QOL. Secondary outcomes were scores on the Modified Barthel Index (MBI) and Beck Depression Inventory (BDI). RESULTS: We did not find any statistically significant differences between the groups in any SF-36 domain including the summaries of physical and mental component. Similarly, the MBI and BDI scores were not significantly different between the groups. CONCLUSION: The effect of paralysis on the dominant hand and QOL in patients with subacute stroke was not significantly different from the effect of paralysis on the non-dominant hand.