Tau positron emission tomography in tauopathies: A narrative review

Aggregation of misfolded tau in the brain is a major pathological feature common in various neurodegenerative disorders known as tauopathies, including Alzheimer’s disease, progressive supranuclear palsy, corticobasal syndrome, and dementia with Lewy bodies. Tauopathies are collection of diseases with varied overlapping symptoms and complicated manifestations. Consequently, it is crucial to be able to assess tau deposits in vivo. Over the past decade, tau-specific radioligands for positron emission tomography (PET) have been developed and tested, including first-generation compounds (e.g., 18F-THK5317, 18F-THK5351, 18F-AV1451, and 11C-PBB3) and second-generation compounds (18F-MK-6240, 18F-RO-948, and 18F-PI-2620). With the recent advances of tau PET tracers, assessing the pattern of tau deposition in vivo is possible. These methods will allow accurate diagnosis of tauopathies and monitoring of disease progression. In this mini review, we summarize current findings from studies using tau PET tracers regarding neuropathological characteristics, clinical implications, and potential applications of tau PET. We also discuss methodological considerations for appropriate use of these technologies and discuss what has been learned from these findings

Effect of proton irradiation on the fluctuation-induced magnetoconductivity of FeSe1−xTex thin films

The influence of proton irradiation on the fluctuation-induced magnetoconductivity of high quality FeSe1−xTex (x=0.4, 0.55) (FST) thin films has been investigated. The measurements were performed with magnetic fields up to 13 T applied in the two main crystal directions. The results were interpreted in terms of the Ginzburg–Landau approach for three-dimensional materials under a total-energy cutoff. The analysis shows that properly-tuned proton irradiation does not appreciably affect fundamental superconducting parameters like the Tc value, the upper critical fields or the anisotropy. This has important consequences from the point of view of possible applications due to the enhancement of vortex pinning induced by irradiation.YSK was supported by the NRF grant funded by the Ministry of Science, ICT and Future Planning (No. NRF-2015M2B2A9028507 and NRF-2016R1A2B4012672). TP was supported by the NRF grant funded by the Ministry of Science, ICT and Future Planning of Korea (No. 2012R1A3A2048816). JM acknowledges support by project FIS2016-79109-P (AEI/FEDER, UE) and by the Xunta de Galicia (project AGRUP 2015/11). SL was supported by the Global Research Network program through the NRF funded by the Ministry of Science and ICT & Future Planning (NRF-2014S1A2A2028361)S

The cortical activation pattern by a rehabilitation robotic hand: a functional NIRS study

Introduction: Clarification of the relationship between external stimuli and brain response has been an important topic in neuroscience and brain rehabilitation. In the current study, using functional near infrared spectroscopy (fNIRS), we attempted to investigate cortical activation patterns generated during execution of a rehabilitation robotic hand. Methods: Ten normal subjects were recruited for this study. Passive movements of the right fingers were performed using a rehabilitation robotic hand at a frequency of 0.5 Hz. We measured values of oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR) and total-hemoglobin (HbT) in five regions of interest: the primary sensory-motor cortex (SM1), hand somatotopy of the contralateral SM1, supplementary motor area (SMA), premotor cortex (PMC), and prefrontal cortex (PFC). Results: HbO and HbT values indicated significant activation in the left SM1, left SMA, left PMC, and left PFC during execution of the rehabilitation robotic hand (uncorrected, p < 0.01). By contrast, HbR value indicated significant activation only in the hand somatotopic area of the left SM1 (uncorrected, p < 0.01). Conclusions: Our results appear to indicate that execution of the rehabilitation robotic hand could induce cortical activation. © 2014 Chang, Lee, Gu, Lee, Jin, Yeo, Seo and Jang.1

Isolation and characterization of equine amniotic membrane-derived mesenchymal stem cells

Recent studies have shown that mesenchymal stem cells (MSCs) are able to differentiate into multi-lineage cells such as adipocytes, chondroblasts, and osteoblasts. Amniotic membrane from whole placenta is a good source of stem cells in humans. This membrane can potentially be used for wound healing and corneal surface reconstruction. Moreover, it can be easily obtained after delivery and is usually discarded as classified waste. In the present study, we successfully isolated and characterized equine amniotic membrane-derived mesenchymal stem cells (eAM-MSCs) that were cultured and maintained in low glucose Dulbeccos modified Eagles medium. The proliferation of eAM-MSCs was measured based on the cumulative population doubling level (CPDL). Immunophenotyping of eAM-MSCs by flow cytometry showed that the major population was of mesenchymal origin. To confirm differentiation potential, a multi-lineage differentiation assay was conducted. We found that under appropriate conditions, eAM-MSCs are capable of multi-lineage differentiation. Our results indicated that eAM-MSCs may be a good source of stem cells, making them potentially useful for veterinary regenerative medicine and cell-based therapy.This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST, 2010-0020265).OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000051105/4SEQ:4PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000051105ADJUST_YN:NEMP_ID:A077262DEPT_CD:551CITE_RATE:1.161FILENAME:2013 jvs 14(2)151-159-equine stem cell.pdfDEPT_NM:수의학과EMAIL:[email protected]_YN:YCONFIRM:

Characterization and clinical application of mesenchymal stem cells from equine umbilical cord blood

Tendinitis of the superficial digital flexor tendon (SDFT) is a significant cause of lameness in horses; however, recent studies have shown that stem cells could be useful in veterinary regenerative medicine. Therefore, we isolated and characterized equine umbilical cord blood mesenchymal stem cells (eUCB-MSCs) from equine umbilical cord blood obtained from thoroughbred mares during the foaling period. Horses that had tendinitis of the SDFT were treated with eUCB-MSCs to confirm the therapeutic effect. After eUCB-MSCs transplantation, the core lesion in the SPIT was found to decrease. These results suggest that transplantation using eUCB-MSCs could be another source of cell treatment.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000051105/7SEQ:7PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000051105ADJUST_YN:YEMP_ID:A077262DEPT_CD:551CITE_RATE:.926FILENAME:2013jvs14(3)367-371-equine stem cell case report.pdfDEPT_NM:수의학과SCOPUS_YN:YCONFIRM:

Utility of Integrated Analysis of Pharmacogenomics and Pharmacometabolomics in Early Phase Clinical Trial: A Case Study of a New Molecular Entity

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials

Caroli's disease misdiagnosed as intraductal papillary neoplasm of the bile duct

Caroli's disease is a rare autosomal-recessive disorder caused by malformation of the ductal plate during embryonic development. Although it is present at birth, Caroli's disease is typically not diagnosed until between the second and fourth decades of life, as it was in the present patient. Here we report a rare case of Caroli's disease limited to one liver segment, which was initially misdiagnosed as an intraductal papillary neoplasm of the bile duct. The asymptomatic patient was treated with liver segmentectomy

Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

Background Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and simultaneous activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step toward clinical application of patient-tailored treatment regimens. Results Toward this goal, we establish a library of 139 gynecologic tumors including epithelial ovarian cancers (EOCs), cervical, endometrial tumors, and uterine sarcomas that are genomically and/or pharmacologically annotated and explore dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discover lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identify TP53 mutation as a molecular determinant that elicits therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identify transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. Conclusions Together, our results demonstrate the potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers