Tetrahydrobiopterin in antenatal brain hypoxia-ischemia-induced motor impairments and cerebral palsy

Antenatal brain hypoxia-ischemia, which occurs in cerebral palsy, is considered a significant cause of motor impairments in children. The mechanisms by which antenatal hypoxia-ischemia causes brain injury and motor deficits still need to be elucidated. Tetrahydrobiopterin is an important enzyme cofactor that is necessary to produce neurotransmitters and to maintain the redox status of the brain. A genetic deficiency of this cofactor from mutations of biosynthetic or recycling enzymes is a well-recognized factor in the development of childhood neurological disorders characterized by motor impairments, developmental delay, and encephalopathy. Experimental hypoxia-ischemia causes a decline in the availability of tetrahydrobiopterin in the immature brain. This decline coincides with the loss of brain function, suggesting this occurrence contributes to neuronal dysfunction and motor impairments. One possible mechanism linking tetrahydrobiopterin deficiency, hypoxia-ischemia, and neuronal injury is oxidative injury. Evidence of the central role of the developmental biology of tetrahydrobiopterin in response to hypoxic ischemic brain injury, especially the development of motor deficits, is discussed

Experimental evaluation of the dosimetric impact of intrafraction prostate rotation using film measurement with a 6DoF robotic arm

Purpose: Tumor motion during radiotherapy can cause a reduction in target dose coverage and an increase in healthy tissue exposure. Tumor motion is not strictly translational and often exhibits complex six degree-of-freedom (6DoF) translational and rotational motion. Although the dosimetric impact of prostate tumor translational motion is well investigated, the dosimetric impact of 6DoF motion has only been studied with simulations or dose reconstruction. This study aims to experimentally quantify the dose error caused by 6DoF motion. The experiment was designed to test the hypothesis that 6DoF motion would cause larger dose errors than translational motion alone through gamma analyses of two-dimensional film measurements. Methods: Four patient-measured intrafraction prostate motion traces and four VMAT 7.25 Gy/Fx SBRT treatment plans were selected for the experiment. The traces represented typical motion patterns, including small-angle rotations (6°). Gafchromic film was placed inside a custom-designed phantom, held by a high-precision 6DoF robotic arm for dose measurements in the coronal plane during treatment delivery. For each combination of the motion trace and treatment plan, two film measurements were made, one with 6DoF motion and the other with the three-dimensional (3D) translation components of the same trace. A gamma pass rate criteria of 2% relative dose/2 mm distance-to-agreement was used in this study and evaluated for each measurement with respect to the static reference film. Two test thresholds, 90% and 50% of the reference dose, were applied to investigate the difference in dose coverage for the PTV region and surrounding areas, respectively. The hypothesis was tested using a Wilcoxon signed-rank test. Results: For each of the 16 plan and motion trace pairs, a reduction in the gamma pass rate was observed for 6DoF motion compared with 3D translational motion. With 90% gamma-test threshold, the reduction was 5.8% ± 7.1% (P < 0.01). With 50% gamma-test threshold, the reduction was 4.1% ± 4.8% (P < 0.01). Conclusion: For the first time, the dosimetric impact of intrafraction prostate rotation during SBRT treatment was measured experimentally. The experimental results support the hypothesis that 6DoF tumor motion causes higher dose error than translation motion alone

Coordination-driven [2+2] metallo-macrocycles isomers: conformational control and photophysical properties

In recent years, fluorescent supramolecular materials have received significant attention due to their wide application prospects. However, the relationship between the conformation of supramolecules and their photophysical properties remains an open question. In this study, two rhomboidal metallacycle isomers, SA and SB, self-assembled with trans- and cis-isomers of tetraphenylethylene-based ditopic pyridyl ligands (LA and LB), and a 120° di-platinum (II) acceptor were prepared. Compared with metallacycle SB constructed by cis- tetraphenylethylene (TPE)-based ligand LB, the curved rhomboidal metallacycle SA constructed with trans-TPE-based ligand LA can restrict molecular motions of the aromatic groups on TPE and exhibits better light-emitting properties. Moreover, curved SA also exhibited better fluorescence stability than isomer SB towards molecules with strongly electron-withdrawing groups. This work provides a new platform to explore the relationship between conformation and the corresponding photophysical properties