Tumor-Specific Expression and Detection of a CEST Reporter Gene

Purpose To develop an imaging tool that enables the detection of malignant tissue with enhanced specificity using the exquisite spatial resolution of MRI. Methods Two mammalian gene expression vectors were created for the expression of the lysine-rich protein (LRP) under the control of the cytomegalovirus (CMV) promoter and the progression elevated gene-3 promoter (PEG-3 promoter) for constitutive and tumor-specific expression of LRP, respectively. Using those vectors, stable cell lines of rat 9L glioma, 9LCMV-LRP and 9LPEG-LRP, were established and tested for CEST contrast in vitro and in vivo. Results 9LPEG-LRP cells showed increased CEST contrast compared with 9L cells in vitro. Both 9LCMV-LRP and 9LPEG-LRP cells were capable of generating tumors in the brains of mice, with a similar growth rate to tumors derived from wild-type 9L cells. An increase in CEST contrast was clearly visible in tumors derived from both 9LCMV-LRP and 9LPEG-LRP cells at 3.4 ppm. Conclusion The PEG-3 promoter:LRP system can be used as a cancer-specific, molecular-genetic imaging reporter system in vivo. Because of the ubiquity of MR imaging in clinical practice, sensors of this class can be used to translate molecular-genetic imaging rapidly

Use of a Y-Shaped Plate for Intermaxillary Fixation

Maxillomandibular fractures usually require intermaxillary fixation as a means to immobilize and stabilize the fracture and to re-establish proper occlusion. Arch bars or intermaxillary fixation screws cannot be used for edentulous patients or for patients who have poor dental health. Here, we present a case of repeated intermaxillary fixation failure in a patient weak alveolar rigidity secondary to multiple dental implants. Because single-point fixation screws were not strong enough to maintain proper occlusion, we have used Y-shaped plates to provide more rigid anchoring points for the intermaxillary wires. We suggest that this method should be considered for patients in whom conventional fixation methods are inappropriate or have failed.N

Use of a Y-Shaped Plate for Intermaxillary Fixation

Maxillomandibular fractures usually require intermaxillary fixation as a means to immobilize and stabilize the fracture and to re-establish proper occlusion. Arch bars or intermaxillary fixation screws cannot be used for edentulous patients or for patients who have poor dental health. Here, we present a case of repeated intermaxillary fixation failure in a patient weak alveolar rigidity secondary to multiple dental implants. Because single-point fixation screws were not strong enough to maintain proper occlusion, we have used Y-shaped plates to provide more rigid anchoring points for the intermaxillary wires. We suggest that this method should be considered for patients in whom conventional fixation methods are inappropriate or have failed.N

MOESM1 of In vitro characterization of pralidoxime transport and acetylcholinesterase reactivation across MDCK cells and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs)

Additional file 1. Table S1

A Unique Core–Shell Structured, Glycol Chitosan-Based Nanoparticle Achieves Cancer-Selective Gene Delivery with Reduced Off-Target Effects

The inherent instability of nucleic acids within serum and the tumor microenvironment necessitates a suitable vehicle for non-viral gene delivery to malignant lesions. A specificity-conferring mechanism is also often needed to mitigate off-target toxicity. In the present study, we report a stable and efficient redox-sensitive nanoparticle system with a unique core–shell structure as a DNA carrier for cancer theranostics. Thiolated polyethylenimine (PEI-SH) is complexed with DNA through electrostatic interactions to form the core, and glycol chitosan-modified with succinimidyl 3-(2-pyridyldithio)propionate (GCS-PDP) is grafted on the surface through a thiolate-disulfide interchange reaction to form the shell. The resulting nanoparticles, GCS-PDP/PEI-SH/DNA nanoparticles (GNPs), exhibit high colloid stability in a simulated physiological environment and redox-responsive DNA release. GNPs not only show a high and redox-responsive cellular uptake, high transfection efficiency, and low cytotoxicity in vitro, but also exhibit selective tumor targeting, with minimal toxicity, in vivo, upon systemic administration. Such a performance positions GNPs as viable candidates for molecular-genetic imaging and theranostic applications

A Series of PSMA-Targeted Near-Infrared Fluorescent Imaging Agents

We have synthesized a series of 10 new, PSMA-targeted, near-infrared imaging agents intended for use in vivo for fluorescence-guided surgery (FGS). Compounds were synthesized from the commercially available amine-reactive active NHS ester of DyLight800. We altered the linker between the PSMA-targeting urea moiety and the fluorophore with a view to improve the pharmacokinetics. Chemical yields for the conjugates ranged from 51% to 86%. The Ki values ranged from 0.10 to 2.19 nM. Inclusion of an N-bromobenzyl substituent at the ε-amino group of lysine enhanced PSMA+ PIP tumor uptake, as did hydrophilic substituents within the linker. The presence of a polyethylene glycol chain within the linker markedly decreased renal uptake. In particular, DyLight800-10 demonstrated high specific uptake relative to background signal within kidney, confirmed by immunohistochemistry. These compounds may be useful for FGS in prostate, renal or other PSMA-expressing cancers

225Ac imaging of NK1-targeted α-particle for glioblastoma radiotherapy

Treatments for glioblastoma (GB) are critically insufficient. We aim to develop an efficient therapy based on a molecularly-specific-delivery of the extremely potent long-lived α particle 225Ac. Substance P (SP) binds neurokinin receptors NK1, overexpressed in GB. Recently, targeted therapies using 90Y- or 213Bi-labeled SPs have emerged as potent options but are either toxic or insufficient. Via 225Ac-SP intracranial delivery, we intend to longitudinally treat GB and eradicate disseminated brain tumors.JRC.E.5-Nuclear chemistr

Evaluation of the Efficacy of COVID-19 Booster Vaccinations in Healthcare Personnel

This study aimed to investigate the efficacy of different COVID-19 booster vaccines by measuring the serum antibody titer. SARS-CoV-2 anti-nucleocapsid protein antibody (N-Ab), anti-spike protein antibody (S-Ab), and neutralizing antibody (Neut.Ab) were measured before and 4–6 weeks after booster vaccinations in healthcare personnel with a previous vaccination within 3–6 months. Personnel who previously received two doses of ChAdOx1 vaccine or two doses of BNT162b2 vaccine received the BNT162b2 vaccine (AAP and PPP groups, respectively). Personnel who previously received two doses of mRNA-1273 received the same vaccine as a booster dose (MMM group). Of the 917 participants, the AAP, MMM, and PPP groups comprised 837 (91.3%), 27 (2.9%), and 53 (5.8%) participants, respectively. The pre-booster S-Ab and Neut.Ab titer were significantly lower in the AAP group. After the booster vaccination, all participants were positive for S-Ab and Neut.Ab; furthermore, the S-Ab and Neut.Ab titer significantly increased in all three groups, although the post-booster S-Ab was lower in the AAP group than in the other groups. The post-booster Neut.Ab titer showed no significant difference among the groups. Our study’s results suggest that booster vaccination, after two prior vaccinations, shows a significant effect regardless of the type of vaccine administered