Long-Term Reliability of Polyimide Electrode Array in Rabbit Retina

Korea Health 21 R&D Project MOHW A050251, NBS-ERC supported by KOSE

Reflections on the Cost of Low-Cost Whole Genome Sequencing: Framing the Health Policy Debate

The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy

High negative predictive value of 68Ga PSMA PET-CT for local lymph node metastases in high risk primary prostate cancer with histopathological correlation

Background: Current guidelines highlight the importance of accurate staging in the management and prognostication of high risk primary prostate cancer. Conventional radiologic imaging techniques are insufficient to reliably detect lymph node metastases in prostate cancer. Despite promising results, there is limited published data on the diagnostic accuracy of PSMA PET-CT to assess local nodal metastases prior to radical prostatectomy. This study aims to assess the diagnostic efficacy of 68Ga PSMA PET-CT in local lymph node staging of high risk primary prostate cancer when compared to histopathological findings following radical prostatectomy with pelvic lymph node dissection. Methods: We retrospectively analysed consecutive patients with high risk primary prostate cancer referred by urologists for primary staging PSMA PET-CT using a 68Ga-labeled PSMA ligand, Glu-NH-CO-NHLys-(Ahx)-[HBEDDCC], from October 2015 to October 2017. The scans of patients who underwent radical prostatectomy with pelvic lymph node dissection were interpreted by the consensus reading of two experienced nuclear medicine physicians blinded to clinical and histopathological data. The contemporaneous records of the referring urologists were retrospectively reviewed for noteworthy unexpected PET findings that altered their personal preference for surgical management. Results: Seventy-one patients were recruited and analysed. PSMA PET-CT showed findings compatible with local disease in 47 patients (66.2%), lymph node metastases in 10 patients (14.1%) and distant metastases in 14 patients (19.7%). Twenty-eight patients (twenty-seven of whom had local disease only) underwent surgery yielding 214 lymph nodes, all of which were negative on histopathological analysis. On a node-based analysis, 213 of 214 lymph nodes were accurately identified as negative for disease with a negative predictive value of 100%. 11 patients had unexpected PET findings contemporaneously documented by urologists to alter their preference for surgical management. Conclusions: PSMA PET-CT appears to have a high negative predictive value for local lymph node metastases in high risk primary prostate cancer when compared to histopathological findings following radical prostatectomy with pelvic lymph node dissection

Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation

The BET proteins are major transcriptional regulators and have emerged as new drug targets, but their functional distinction has remained elusive. In this study, we report that the BET family members Brd2 and Brd4 exert distinct genomic functions at genes whose transcription they co-regulate during mouse T-helper 17 (Th17) cell differentiation. Brd2 is associated with the chromatin insulator CTCF and the cohesin complex to support cis-regulatory enhancer assembly for gene transcriptional activation. In this context, Brd2 binds the transcription factor Stat3 in an acetylation-sensitive manner and facilitates Stat3 recruitment to active enhancers occupied with transcription factors Irf4 and Batf. In parallel, Brd4 temporally controls RNA polymerase II (Pol II) processivity during transcription elongation through cyclinT1/Cdk9 recruitment and Pol II Ser2 phosphorylation. Collectively, our study uncovers both separate and interdependent Brd2 and Brd4 functions in potentiating the genetic program required for Th17 cell development and adaptive immunity., , Cheung et al. uncover both separate and interdependent Brd2 and Brd4 genomic functions in potentiating the genetic program required for Th17 cell development and adaptive immunity. Brd2 interacts with transcription factor Stat3 and chromatin insulator CTCF/cohesin complex to support enhancer assembly, whereas Brd4 temporally controls RNA PolII for transcription elongation

Renal cement embolism during percutaneous vertebroplasty

Percutaneous vertebroplasty (PVP) is an effective treatment for lesions of the vertebral body that involves a percutaneous injection of polymethylmethacrylate (PMMA). Although PVP is considered to be minimally invasive, complications can occur during the procedure. We encountered a renal embolism of PMMA in a 57-year-old man that occurred during PVP. This rare case of PMMA leakage occurred outside of the anterior cortical fracture site of the L1 vertebral body, and multiple tubular bone cements migrated to the course of the renal vessels via the valveless collateral venous network surrounding the L1 body. Although the authors could not explain the exact cause of the renal cement embolism, we believe that physicians should be aware of the fracture pattern, anatomy of the vertebral venous system, and careful fluoroscopic monitoring to minimize the risks during the PVP

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

Sequence Defined Disulfide-Linked Shuttle for Strongly Enhanced Intracellular Protein Delivery

Intracellular protein transduction technology is opening the door for a promising alternative to gene therapy. Techniques have to address all critical steps, like efficient cell uptake, endolysosomal escape, low toxicity, while maintaining full functional activity of the delivered protein. Here, we present the use of a chemically precise, structure defined three-arm cationic oligomer carrier molecule for protein delivery. This carrier of exact and low molecular weight combines good cellular uptake with efficient endosomal escape and low toxicity. The protein cargo is covalently attached by a bioreversible disulfide linkage. Murine 3T3 fibroblasts could be transduced very efficiently with cargo nlsEGFP, which was tagged with a nuclear localization signal. We could show subcellular delivery of the nlsEGFP to the nucleus, confirming cytosolic delivery and expected subsequent subcellular trafficking. Transfection efficiency was concentration-dependent in a directly linear mode and 20-fold higher in comparison with HIV-TAT-nlsEGFP containing a functional TAT transduction domain. Furthermore, β-galactosidase as a model enzyme cargo, modified with the carrier oligomer, was transduced into neuroblastoma cells in enzymatically active form

Suppression of EAE and Prevention of Blood-Brain Barrier Breakdown after Vaccination with Novel Bifunctional Peptide Inhibitor

The efficacy of bifunctional peptide inhibitor (BPI) in preventing blood-brain barrier (BBB) breakdown during onset of experimental autoimmune encephalomyelitis (EAE) and suppression of the disease was evaluated in mice. The mechanism that defines how BPI prevents the disease was investigated by measuring the in vitro cytokine production of splenocytes. Peptides were injected 5 to 11 days prior to induction of EAE, and the severity of the disease was monitored by a standard clinical scoring protocol and change in body weight. The BBB breakdown in diseased and treated mice was compared to that in normal control mice by determining deposition of gadolinium diethylenetriaminepentaacetate (Gd-DTPA) in the brain using magnetic resonance imaging (MRI). Mice treated with PLP-BPI showed no or low indication of EAE as well as normal increase in body weight. In contrast, mice treated with the control peptide or PBS showed a decrease in body weight and a high disease score. The diseased mice had high deposition of Gd-DTPA in the brain, indicating breakdown in the BBB. However, the deposition of Gd-DTPA in PLP-BPI-treated mice was similar to that in normal control mice. Thus, PLP-BPI can suppress EAE when administered as a peptide vaccine and maintain the integrity of the BBB