Background and Objective
We developed a quantitative method to measure movement representations of a phantom upper limb using a bimanual circle‐line coordination task (BCT). We investigated whether ...short‐term neurorehabilitation with a virtual reality (VR) system would restore voluntary movement representations and alleviate phantom limb pain (PLP).
Methods
Eight PLP patients were enrolled. In the BCT, they repeatedly drew vertical lines using the intact hand and intended to draw circles using the phantom limb. Drawing circles mentally using the phantom limb led to the emergence of an oval transfiguration of the vertical lines (‘bimanual‐coupling’ effect). We quantitatively measured the degree of this bimanual‐coupling effect as movement representations of the phantom limb before and immediately after short‐term VR neurorehabilitation. This was achieved using an 11‐point numerical rating scale (NRS) for PLP intensity and the Short‐Form McGill Pain Questionnaire (SF‐MPQ). During VR neurorehabilitation, patients wore a head‐mounted display that showed a mirror‐reversed computer graphic image of an intact arm (the virtual phantom limb). By intending to move both limbs simultaneously and similarly, the patients perceived voluntary execution of movement in their phantom limb.
Results
Short‐term VR neurorehabilitation promptly restored voluntary movement representations in the BCT and alleviated PLP (NRS: p = 0.015; 39.1 ± 28.4% relief, SF‐MPQ: p = 0.015; 61.5 ± 48.5% relief). Restoration of phantom limb movement representations and reduced PLP intensity were linearly correlated (p < 0.05).
Conclusions
VR rehabilitation may encourage patient's motivation and multimodal sensorimotor re‐integration of a phantom limb and subsequently have a potent analgesic effect.
Significance
There was no objective evidence that restoring movement representation by neurorehabilitation with virtual reality alleviated phantom limb pain. This study revealed quantitatively that restoring movement representation with virtual reality rehabilitation using a bimanual coordination task correlated with alleviation of phantom limb pain.
Highlights • We examine 3D printing in the context of urologic oncology. • Patient-specific 3D printed kidney and prostate tumor models were created. • 3D printed models extend the current ...capabilities of conventional 3D visualization. • 3D printed models may be used for surgical planning and intraoperative guidance.
Involvement of the aryl hydrocarbon receptor (AHR) in carcinogenesis has been suggested in many studies. Upregulation of AHR has been reported in some cancer species, and an association between ...single-nucleotide polymorphisms (SNPs) of AHR and cancer risk or cancer development has also been reported. This evidence suggests the involvement of some specific SNPs in AHR transcriptional regulation in the process of carcinogenesis or cancer development, but there have been no studies to elucidate the mechanism involved. In this study, we identified the transcription factor Nuclear Factor 1-C (NF1C) as a candidate to regulate AHR transcription in a polymorphism-dependent manner. SNP rs10249788 was included in a consensus binding site for NF1C. Our results suggested that NF1C preferred the C allele to the T allele at rs10249788 for binding. Forced expression of NF1C suppressed the activity of the AHR promoter with C at rs10249788 stronger than that with T. Moreover, expression analysis of human uterine endometrial cancer (HEC) specimens showed greater upregulation of AHR and downregulation of NF1C than those of normal endometrium specimens. Sequence analysis showed HEC patients at advanced stages tended to possess T/T alleles more frequently than healthy women. We also demonstrated that NF1C suppressed proliferation, motility and invasion of HEC cells. This function was at least partially mediated by AHR. This study is the first to report that a polymorphism on the AHR regulatory region affected transcriptional regulation of the AHR gene in vitro. Because NF1C is a tumor suppressor, our new insights into AHR deregulation and its polymorphisms could reveal novel mechanisms of genetic susceptibility to cancer.
Facial allotransplantation replaces missing facial structures with anatomically identical tissues, providing desired functional, esthetic, and psychosocial benefits far superior to those of ...conventional methods. On the basis of very encouraging initial results, it is likely that more procedures will be performed in the near future. Typical candidates have extremely complex vascular anatomy due to severe injury and/or multiple prior reconstructive attempts; thus, each procedure is uniquely determined by the defects and vascular anatomy of the candidate. We detail CT angiography vascular mapping, noting the clinical relevance of the imaging, the angiosome concept and noninvasive delineation of the key vessels, and current controversies related to the vascular anastomoses.
Aims: Squamous cell carcinoma (SCC) is the most common form of malignant transformation in mature cystic teratoma (MCT) of the ovary. Some investigators have suggested the possibility of origin from ...columnar epithelium. The aim of this study was to analyse such tumours immunohistochemically to elucidate their histogenesis.
Methods and results: The expression of cytokeratin (CK) 10 and CK18 was examined in 21 samples of SCC arising in MCT. The expression of CK10 and CK18 was also assessed in SCCs arising in different organs (skin, vulva, lung and uterine cervix) for the purpose of comparison. SCC in MCT expressed CK10 in 7/21 cases 33.3%, 95% confidence interval (CI) 0.12–0.53 and CK18 in 14/21 cases (66.7%, 95% CI 0.46–0.87). SCC in MCT expressed CK10 less frequently, but CK18 more frequently, as is the case in SCCs of the uterine cervix (CK10, 20%; CK18, 70%) and the lung (CK10, 5%; CK18, 90%), both of which are derived from columnar epithelium by squamous metaplasia.
Conclusions: SCC in MCT may be derived from metaplastic squamous epithelium.
Low level, antenatal exposure to dioxins is associated with low birth weight, which in turn is associated with long-term sequelae. We exposed the human extravillous cytotrophoblast (EVT) lines ...HTR-8/SV40 and TCL1 to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and assessed cell growth, invasion, and differentiation. TCDD had no effect on cell proliferation, invasion, or tube formation in Matrigel. The EVT-derived cells expressed a functional aryl hydrocarbon receptor protein; however, TCDD exposure did not alter expression levels of proteins involved in EVT differentiation in early pregnancy, including hypoxia-inducible factor 1A (HIF1A), vascular endothelial growth factor (VEGF), Integrin A1, A6, and AVB3. These results suggest that the reduction in fetal weight induced by dioxin is not the result of vascular remodeling via EVT dysfunction.
Abstract Extravillous trophoblast (EVT) cells mimic endothelial cells during angiogenesis, inducing remodeling of the spiral arteries that increases blood flow toward the intravillous space. We have ...previously shown that signals involving the vascular endothelial growth factor (VEGF) axis are essential for endovascular differentiation through integrin signaling from the extracellular matrix: This was accomplished with use of the human EVT cell line TCL1, which shows tube formation that specifically recalls morphological changes in endothelial cells. To investigate endovascular differentiation in EVT further, we investigated the role of hypoxia inducible factor (HIF)1A, a subunit of HIF1 transcription factor that regulates not only adaptive responses to hypoxia, but also many cellular functions under normoxia, which was up-regulated in DNA microarray analysis during matrigel-induced endovascular differentiation under normoxia. HIF1A induces VEGF and ITGAV/ITGB3 aggregation, actions known to be important for cellular survival and endovascular differentiation in EVT. Inhibition of HIF1A up-regulation using siRNA introduction or chemical inhibition suppressed hypoxia-responsive element transcriptional activity, VEGF induction, ITGAV/ITGB3 aggregation accompanied by the inhibition of tube formation in TCL1 cells. These results suggest that HIF1A has a crucial role in regulating EVT behavior including matrigel-induced endovascular differentiation under normoxia.
Imprinting within domains occurs through epigenetic alterations to imprinting centers (ICs) that result in the establishment of parental-specific differences in gene expression. One candidate IC lies ...within the imprinted domain on human chromosome region 6q24. This domain contains two paternally expressed genes, the zinc finger protein gene PLAGL1 (ZAC/LOT1) and an untranslated mRNAcalled HYMAI. The putative IC overlaps exon 1 of HYMAI and is differentially methylated in somatic tissues. In humans, loss of methylation within this region is seen in some patients with transient neonatal diabetes mellitus, and hypermethylation of this region is found in ovarian cancer and is associated with changes in expression of PLAGL1, suggesting that it plays a key role in regulating gene expression. Differential methylation within this region is conserved in the homologous region on mouse chromosome 10A and is present on the maternal allele. In this paper, we report that DNA methylation is established during the growth phase of oogenesis and that this coincides with the establishment of monoallelic expression from this region lending further support to the hypothesis that this region functions as an IC.
Several proteins, including transforming growth factor beta (TGF-beta) receptor type I (RI), TGF-beta receptor type II (RII), Smad2, Smad3, and Smad4/DPC4, have been identified in the transduction ...pathway of the tumor suppressor TGF-beta. Mutations in TGF-beta RI, TGF-beta RII, Smad2, and Smad4/DPC4 genes are associated with several human cancers. The present study examines these gene mutations in 32 human ovarian cancers and 14 patient-matched normal tissues. For the first time, mutations in the Smad2 and Smad4 genes were analyzed in relation to human ovarian cancer. Gene mutations of TGF-beta RI, TGF-beta RII, Smad2, and Smad4 were analyzed using specific primers by PCR-single-strand conformational polymorphism (SSCP), and the results revealed a frameshift mutation at codons 276-277 (CTCTGG-->CTGCGTGG) in exon 5 of TGF-beta RI in 10 of 32 tumor samples (31.3%). This mutation was associated with reduced or absent expression of TGF-beta RI protein and p53 protein in tumor tissues. We detected SSCP variants of TGF-beta RII in exon 2 in 20 of 32 tumors. Sequence analysis of these variants revealed an A to G transition at the seventh band of intron 2. In this A to G polymorphism in intron 2, 12 samples (37.5%) had A/A alleles, 12 (37.5%) had A/G alleles, and 8 (25%) had G/G alleles. We detected Smad2 SSCP variants in exon 4 in 12 of 32 tumors (37.5%). Sequence analysis revealed a 2-bp deletion in the polypyrimidine tract of intron 3, which is located at position -39 to -56 in the splice acceptor site of the intron 3-exon 4 junction. No SSCP variants were detected in the Smad4 gene. These findings suggest that mutations in the TGF-beta RI and in its signal transduction pathway are likely responsible for human ovarian carcinogenesis.
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