Preemptive application of QX-314 attenuates trigeminal neuropathic mechanical allodynia in rats.

The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.

Management of Gestational Gigantomastia with Goldilocks Procedure after Mastectomy: A Case Report and Review of Literature.

Gestational gigantomastia is characterized by the rapid growth of breasts during pregnancy. The treatment method of gestational gigantomastia is unclear; if the medical treatment is ineffective, surgery is considered. However, sufficient research on which method is best to perform breast reconstruction for the gestational gigantomastia patient has not yet been conducted. Our patient was young and had aesthetic needs; thus, we did not recommend modified radical mastectomy. However, it was difficult for the patient to consider active reconstruction using an implant or autologous tissue because of the expected complications and economic problems. The patient had a thin body shape and very large breasts compared with the trunk. Therefore, breast volume was not significantly required after reconstruction. Additionally, we expected that a considerable portion of skin would remain after mastectomy as a tubular-shaped breast. It was expected that the Goldilocks technique would be sufficient to meet the patient's volume needs. Therefore, we proceeded with total mastectomy and reconstruction using the Goldilocks procedure. No complications were recorded after the operation; most of the patient's discomfort was resolved, and the shape and size of the breasts were satisfactory.

Posterior corneal shape changes in myopic overnight orthokeratology.

PURPOSE: To evaluate changes in the shape of the posterior cornea at the end of the day based on anterior corneal topography and corneal thickness during myopic overnight orthokeratology (OK) over 14 nights' wear of reverse geometry gas-permeable (GP) contact lenses. METHODS: Eighteen subjects (aged 19 to 32 years) with low myopia and astigmatism were fitted with reverse geometry lenses (BE; Capricornia Contact Lens Pty Ltd) for myopic OK, which were worn overnight only for a 14-day period. A separate group of 10 subjects (aged 19 to 32 years) with low astigmatism wore J-Contour conventional GP lenses (Capricornia Contact Lens Pty Ltd) for one night. Corneal topography (Medmont E-300) and total corneal thickness (Holden-Payor optical pachometer) across the horizontal meridian were measured at baseline and approximately 8 to 10 hours after lens removal on days 1, 4, 7, and 14 of overnight OK lens wear and after one night of GP lens wear for the control group. Posterior corneal apical radius of curvature and asphericity (Q) were calculated using an in-house program based on the anterior corneal ellipse curve and corneal thickness. RESULTS: Myopia reduced from -2.64 ± 0.99 diopters (mean ± SD) to -0.39 ± 0.49 diopters during 14 days of overnight OK lens wear. In the OK lens-wearing eyes, there were no statistically significant changes in posterior corneal apical radius of curvature during 14 days of overnight OK. However, there were statistically significant increases in posterior corneal Q on days 4 and 7. In the conventional GP lens-wearing eyes, there were no statistically significant changes in either posterior corneal apical radius or Q after overnight lens wear. CONCLUSIONS: The results of this study support the current hypothesis that the OK refractive effect is achieved primarily through remodeling of the anterior corneal layers, without overall corneal bending.

A detailed understanding of the electronic bipolar resistance switching behavior in Pt/TiO2/Pt structure.

The detailed mechanism of electronic bipolar resistance switching (BRS) in the Pt/TiO(2)/Pt structure was examined. The conduction mechanism analysis showed that the trap-free and trap-mediated space-charge-limited conduction (SCLC) governs the low and high resistance state of BRS, respectively. The SCLC was confirmed by fitting the current-voltage characteristics of low and high resistance states at various temperatures. The BRS behavior originated from the asymmetric potential barrier for electrons escaping from, and trapping into, the trap sites with respect to the bias polarity. This asymmetric potential barrier was formed at the interface between the trap layer and trap-free layer. The detailed parameters such as trap density, and trap layer and trap-free layer thicknesses in the electronic BRS were evaluated. This showed that the degradation in the switching performance could be understood from the decrease and modified distribution of the trap densities in the trap layer.

Electrically configurable electroforming and bipolar resistive switching in Pt/TiO2/Pt structures.

This study examined the effects of electrical forming methods on the bipolar resistance switching (BRS) behavior in Pt/TiO(2)/Pt sandwich structures. The BRS is confined to a region near the ruptured end of conducting nanofilaments, which are composed of a Ti(n)O(2n-1) Magnéli phase formed by electroforming. The intermediate phase with an oxygen vacancy concentration between the insulating TiO(2) and the residual conducting filament that formed at the interface region was considered to be the switching layer (SL). The change in filament shape caused by a variation in the compliance current during filament formation resulted in a different filament rupture location and SL configuration. Precise control of the filament formation and rupture process resulted in SLs connected in an anti-parallel configuration. It was possible to reconfigure the SLs in the same fashion without any restraints, which allowed an unlimited memristive operation to be achieved. This paper presents a new technique in voltage sweep mode that applies a compliance current as a tool to achieve a memristor with unlimited operation.

Embryonic Fibroblasts Promote Antitumor Cytotoxic Effects of CD8+ T Cells.

Adoptive CD8+ T cell therapy has emerged as an important modality for the treatment of cancers. However, the significant drawback of transfused T cells is their poor survival and functionality in response to tumors. To overcome this limitation, an important consideration is exploring a culture condition to generate superior antitumor cytotoxic T lymphocytes (CTLs) for adoptive therapy. Here, we provide a novel approach to generate potent CTL clones in mouse embryonic fibroblast-conditioned medium (MEF-CM). We found CTLs derived with MEF-CM have higher potential in long-term persistence in tumor bearing and non-tumor-bearing mice. Importantly, adoptive transfer of MEF-CM-cultured CTLs dramatically regressed tumor growth and prolonged mice survival. Characterization of MEF-CM-cultured CTLs (effector molecules, phenotypes, and transcription factors) suggests that MEF-CM enhances the effector functions of CD8+ T cells in part by the upregulation of the T-box transcription factor eomesodermin. Consequently, MEF-CM enhances the intrinsic qualities of effector CD8+ T cells to augment antitumor immunity.

Age-dependent changes of gene expression in the Drosophila head.

Previous gene expression profiling studies in Drosophila have provided clues for understanding the aging process at the gene expression level. For a detailed understanding, studies of specific regions of the body are necessary. We therefore employed microarray analysis to examine gene expression changes in the Drosophila head during aging. Six hundred and eighty-four of the 5405 genes present in the microarray showed significant age-dependent changes as determined by significance analysis of microarray (SAM) (q < 0.05). The biological significance of the changes was analyzed using the gene annotations provided by the Gene Ontology Consortium. Major changes involved genes affecting energy metabolism (proton transport, energy pathways, oxidative phosphorylation) and neuronal function, especially responses to light. Genes involved in protein catabolism and several other metabolic processes also showed age-dependent changes. Most of the changes were reductions in gene expression and occurred before day 13 of adult life. After day 13, the age-dependent gene expression changes were relatively smaller than earlier life. Interestingly, the two biological processes of major gene expression changes are related to the two known environmental changes that increase life span in Drosophila: caloric restriction and light reduction. Our findings suggest that light signaling and energy metabolism may be important biological processes affected by aging and be interesting targets for the further investigation related to the longevity in Drosophila.

Effect of dissolved metal ions on PCE decomposition by gamma-rays.

This study investigates the effect of initial tetrachloroethylene (PCE) concentration, irradiation dose and dissolved metal ions such as Cr3+, Mn2+, Fe3+, Co2+, Ni2+, Cu2+ and Zn2+ on removal of PCE by gamma irradiation. The amount of removed PCE decreased with increase in initial PCE concentration and increased with increase in irradiation dose. PCE removal reached a maximum in the presence of Fe3+, while Cu2+ strongly hindered PCE decomposition. Except for Cu2+, the amount of removed PCE in the presence of metal ions was linearly dependent on the standard reduction potential of the metal ions. The extraordinary inhibition of Cu2+ in PCE removal was caused by the action of Cu2+ as a strong *OH scavenger, that was directly confirmed by electron paramagnetic resonance spectroscopy.

Effect of different bone marrow stimulation techniques (BSTs) on MSCs mobilization.

The therapeutic effect of bone marrow stimulation techniques (BSTs) is mainly attributed to the role of mesenchymal stem cells (MSCs) from the bone marrow. However, no studies have directly shown the amount of MSCs drained by BSTs. This study hypothesized that differences in the opening of subchondral bone affect the number of MSCs drained from the bone marrow. We purposed that as the exposed area and hole size of BSTs vary, the number of MSCs drained out was measured. Three groups of different BSTs were designed that have variations in the sizes of total exposed area and individual holes. Three different BSTs using a curette, 1.5- and 0.8-mm awls were carried out on the full-thickness femoral cartilage defect of young rabbits. After BST, the number of MSCs in the blood clot was measured by CFU-Fs assay. As the size of the total exposed area increased, so did the number of MSCs obtained. The number of MSCs drained from bone marrow may vary depending on different BSTs and this could affect therapeutic efficacy of cartilage defect. As current microfracture (MF) method cannot drain the most MSCs clinically, more improved surgery technique is needed.

The maturity of tissue-engineered cartilage in vitro affects the repairability for osteochondral defect.

Cartilage tissue engineering using cells and biocompatible scaffolds has emerged as a promising approach to repair of cartilage damage. To date, however, no engineered cartilage has proven to be equivalent to native cartilage in terms of biochemical and compression properties, as well as histological features. An alternative strategy for cartilage engineering is to focus on the in vivo regeneration potential of immature engineered cartilage. Here, we used a rabbit model to evaluate the extent to which the maturity of engineered cartilage influenced the remodeling and integration of implanted extracellular matrix scaffolds containing allogenous chondrocytes. Full-thickness osteochondral defects were created in the trochlear groove of New Zealand white rabbits. Left knee defects were left untreated as a control (group 1), and right knee defects were implanted with tissue-engineered cartilage cultured in vitro for 2 days (group 2), 2 weeks (group 3), or 4 weeks (group 4). Histological, chemical, and compression assays of engineered cartilage in vitro showed that biochemical composition became more cartilagenous, and biomechanical property for compression gradually increased with culture time. In an in vivo study, gross imaging and histological observation at 1 and 3 months after implanting in vitro-cultured engineered cartilage showed that defects in groups 3 and 4 were repaired with hyaline cartilage-like tissue, whereas defects were only partially filled with fibrocartilage after 1 month in groups 1 and 2. At 3 months, group 4 showed striking features of hyaline cartilage tissue, with a mature matrix and a columnar arrangement of chondrocytes. Zonal distribution of type II collagen was most prominent, and the International Cartilage Repair Society score was also highest at this time. In addition, the subchondral bone was well ossified. In conclusion, in vivo engineered cartilage was remodeled when implanted; however, its extent to maturity varied with cultivation period. Our results showed that the more matured the engineered cartilage was, the better repaired the osteochondral defect was, highlighting the importance of the in vitro cultivation period.

Downregulation of lipopolysaccharide response in Drosophila by negative crosstalk between the AP1 and NF-kappaB signaling modules.

IkappaB kinase (IKK) and Jun N-terminal kinase (Jnk) signaling modules are important in the synthesis of immune effector molecules during innate immune responses against lipopolysaccharide and peptidoglycan. However, the regulatory mechanisms required for specificity and termination of these immune responses are unclear. We show here that crosstalk occurred between the drosophila Jnk and IKK pathways, which led to downregulation of each other's activity. The inhibitory action of Jnk was mediated by binding of drosophila activator protein 1 (AP1) to promoters activated by the transcription factor NF-kappaB. This binding led to recruitment of the histone deacetylase dHDAC1 to the promoter of the gene encoding the antibacterial protein Attacin-A and to local modification of histone acetylation content. Thus, AP1 acts as a repressor by recruiting the deacetylase complex to terminate activation of a group of NF-kappaB target genes.

Novel Mediator proteins of the small Mediator complex in Drosophila SL2 cells.

The Mediator complex is generally required for transcriptional regulation in species ranging from yeast to human. Throughout evolution, the functional diversity of the Mediator complex has been enhanced to meet the increasing requirements for sophisticated gene regulation. It is likely that greater structural complexity is thus required to accomplish these new, complex regulatory functions. In this study, we took systematic steps to examine various types of Mediator complexes in Drosophila melanogaster. Such efforts led to the identification of three distinct forms of Mediator complexes. In exploring their compositional and functional heterogeneity, we found that the smallest complex (C1) is highly enriched in a certain type of Drosophila cells and possesses novel Mediator proteins. The subunits shared among the three Mediator complexes (C1, C2, and C3) appear to form a stable modular structure that serves as a binding surface for transcriptional activator proteins. However, only C2 and C3 were able to support activated transcription in vitro. These findings suggest that different cell types may require distinct Mediator complexes, some of which may participate in nuclear processes other than the previously identified functions.