The aim of this study was to evaluate the long-term survival of craniofacial implants and prostheses and to identify factors associated with failure in a cohort of patients. A 25-year retrospective ...analysis was conducted at Royal Melbourne Hospital. Data included demographic characteristics, age, site and cause of the deformity, and number and survival of implants. Odds ratios were calculated and event-to-time Kaplan–Meier analyses performed. One hundred and ten patients were included (341 implants); their mean age was 46.2 years. The overall implant survival rate was 79.5% (mean follow-up 10.6 years). Temporal implants had the highest success rate (97.0%), followed by nasal implants (87.5%) and orbital implants (63.3%); differences were statistically significant (P<0.0001 and P=0.033, respectively). Kaplan–Meier analyses to determine long-term implant and prosthesis survival found temporal implants had the highest prosthetic (P<0.0001) and implant survival (P<0.0001). Patients with congenital deformities demonstrated the highest success rate. Radiotherapy was found to increase the risk of implant failure (P=0.02). Craniofacial implant-retained prostheses are a reliable and effective option for the restoration of facial defects, with good long-term success rates. Orbital implants and those placed post oncological surgery have a higher failure rate.
Pancreatic stellate cells (PSC), a prominent stromal cell, contribute to the progression of pancreatic ductal adenocarcinoma (PDAC). We aim to investigate the mechanisms by which PSC promote cell ...proliferation in PDAC cell lines, BxPC-3 and AsPC-1. PSC-conditioned media (PSC-CM) induced proliferation of these cells in a dose- and time-dependent manner. Nrf2 protein was upregulated and subsequently, its transcriptional activity was increased with greater DNA binding activity and transcription of target genes. Downregulation of Nrf2 led to suppression of PSC-CM activity in BxPC-3, but not in AsPC-1 cells. However, overexpression of Nrf2 alone resulted in increased cell proliferation in both cell lines, and treatment with PSC-CM further enhanced this effect. Activation of Nrf2 pathway resulted in upregulation of metabolic genes involved in pentose phosphate pathway, glutaminolysis and glutathione biosynthesis. Downregulation and inhibition of glucose-6-phosphate-dehydrogenase with siRNA and chemical approaches reduced PSC-mediated cell proliferation. Among the cytokines present in PSC-CM, stromal-derived factor-1 alpha (SDF-1α) and interleukin-6 (IL-6) activated Nrf2 pathway to induce cell proliferation in both cells, as shown with neutralization antibodies, recombinant proteins and signaling inhibitors. Taken together, SDF-1α and IL-6 secreted from PSC induced PDAC cell proliferation via Nrf2-activated metabolic reprogramming and ROS detoxification.
Extracellular signal-regulated kinase (ERK) is a versatile protein kinase, which has been implicated in signaling numerous biological functions ranging from embryonic development to memory formation. ...Recent reports, including ours, indicate that ERK plays a central role in promoting neuronal degeneration in various neuronal systems including neurodegenerative diseases. Mechanisms involved in ERK-induced neuronal degeneration are beginning to emerge. In this review, we summarize evidence suggesting ERK to be a predominant inducer of a non-apoptotic mode of neuronal death. Further, we discuss the mechanisms and the putative molecular inter-players associated with ERK-mediated neuronal death.
Glioblastoma can originate from terminally differentiated astrocytes and neurons, which can dedifferentiate to a stem cell-like state upon transformation. In this study, we confirmed that transformed ...dedifferentiated astrocytes and neurons acquired a stem/progenitor cell state, although they still retained gene expression memory from their parental cell. Transcriptional network analysis on these cells identified upregulated genes in three main pathways: Wnt signaling, cell cycle and focal adhesion with the gene Spp1, also known as osteopontin (OPN) serving as a key common node connecting these three pathways. Inhibition of OPN blocked the formation of neurospheres, affected the proliferative capacity of transformed neurons and reduced the expression levels of neural stem cell markers. Specific inhibition of OPN in both murine and human glioma tumors prolonged mice survival. We conclude that OPN is an important player in dedifferentiation of cells during tumor formation, hence its inhibition can be a therapeutic target for glioblastoma.
Artemisia vulgaris L. belongs to Asteraceae, is a herbal plant that has various benefits in the medical field, so that its use in the medical field can be explored optimally, the plant must be ...thoroughly identified. This study aims to identify A. vulgaris both in terms of descriptive morpho-anatomy and DNA barcoding using BLAST and phylogenetic tree reconstruction. The morpho-anatomical character was observed on root, stem, and leaf. DNA barcoding analysis was carried out through amplification and alignment of the rbcL and matK genes. All studies were conducted on three samples from Taman Husada (Medicinal Plant Garden) Graha Famili Surabaya, Indonesia. The anatomical slide was prepared by the paraffin method. Morphological studies revealed that the leaves of A. vulgaris both on the lower-middle part and on the upper part of the stem have differences, especially in the character of the stipules, petioles, and incisions they have. Meanwhile, from the study of anatomy, A. vulgaris has an anomocytic type of stomata and its distribution is mostly on the ventral part of the leaves. Through the BLAST process and phylogenetic tree reconstruction, the plant sequences being studied are closely related to several species of the genus Artemisia as indicated by a percentage identity above 98% and branch proximity between taxa in the reconstructed phylogenetic tree.
Strategies for the determination of 3D structures of biological macromolecules using electron crystallography and single-particle electron microscopy utilize powerful tools for the averaging of ...information obtained from 2D projection images of structurally homogeneous specimens. In contrast, electron tomographic approaches have often been used to study the 3D structures of heterogeneous, one-of-a-kind objects such as whole cells where image-averaging strategies are not applicable. Complex entities such as cells and viruses, nevertheless, contain multiple copies of numerous macromolecules that can individually be subjected to 3D averaging. Here we present a complete framework for alignment, classification, and averaging of volumes derived by electron tomography that is computationally efficient and effectively accounts for the missing wedge that is inherent to limited-angle electron tomography. Modeling the missing data as a multiplying mask in reciprocal space we show that the effect of the missing wedge can be accounted for seamlessly in all alignment and classification operations. We solve the alignment problem using the convolution theorem in harmonic analysis, thus eliminating the need for approaches that require exhaustive angular search, and adopt an iterative approach to alignment and classification that does not require the use of external references. We demonstrate that our method can be successfully applied for 3D classification and averaging of phantom volumes as well as experimentally obtained tomograms of GroEL where the outcomes of the analysis can be quantitatively compared against the expected results.
Uterine Fibroids, or leiomyomata, affect millions of women world-wide, with a high incidence of 75% within women of reproductive age. In ~30% of patients, uterine fibroids cause menorrhagia, or heavy ...menstrual bleeding, and more than half of the patients experience symptoms such as heavy menstrual bleeding, pelvic pain, or infertility. Treatment is symptomatic with limited options including hysterectomy as the most radical solution. The genetic foundations of uterine fibroid growth have been traced to somatic driver mutations (
MED12, HMGA2, FH
−/−
, and
COL4A5-A6
). These also lead to downstream expression of angiogenic factors including IGF-1 and IGF-2, as opposed to the VEGF-driven mechanism found in the angiogenesis of hypoxic tumors. The resulting vasculature supplying the fibroid with nutrients and oxygen is highly irregular. Of particular interest is the formation of a pseudocapsule around intramural fibroids, a unique structure within tumor angiogenesis. These aberrations in vascular architecture and network could explain the heavy menstrual bleeding observed. However, other theories have been proposed such as venous trunks, or venous lakes caused by the blocking of normal blood flow by uterine fibroids, or the increased local action of vasoactive growth factors. Here, we review and discuss the evidence for the various hypotheses proposed.
In Lagrangian–Eulerian (LE) simulations of two-way coupled particle-laden flows, the dispersed phase is represented either by real particles or by computational particles. In traditional LE (TLE) ...simulations, each computational particle is assigned a constant statistical weight, which is defined as the expected number of real particles represented by a computational particle. If the spatial distribution of particles becomes highly non-uniform due to particle–fluid or particle–particle interactions, then TLE simulations fail to yield numerically converged solutions due to high statistical error in regions with few particles. In this work, a particle-laden lid-driven cavity flow is solved on progressively refined grids to demonstrate the inability of TLE simulations to yield numerically converged estimates for the mean interphase momentum transfer term. We propose an improved LE simulation (ILE) method that remedies the above limitation of TLE simulations. In the ILE method, the statistical weights are evolved such that the same physical problem is simulated, but the number density of computational particles is maintained near-uniform throughout the simulation, resulting in statistical error that remains nearly constant with grid refinement. The evolution of statistical weights is rigorously justified by deriving the consistency conditions arising from the requirement that the resulting computational ensemble correspond to a statistical description of the same physical problem with real particles. The same particle-laden lid-driven cavity flow is solved on progressively refined grids to demonstrate the ability of ILE simulation to achieve numerically converged estimates for the mean interphase momentum transfer term. The
accuracy of the ILE method is quantified using a test problem that admits an analytical solution for the mean interphase momentum transfer term. In order to improve the accuracy of numerical estimates of the mean interphase momentum transfer term, an improved estimator is proposed to replace the conventional estimator. The improved estimator results in more accurate estimates that converge faster than those obtained using the conventional estimator. The ILE simulation method along with the improved estimator is recommended for accurate and numerically convergent LE simulations.
Abstract Paediatric odontogenic myxoma (OM) is a rare pathological condition in the oral and maxillofacial region. There has been much debate in the literature regarding the preferred method of ...treatment; however due to the rare nature of this disease, definitive algorithms of management are yet to be determined. A case series of eight paediatric patients with OM is presented. Six of the lesions were in the maxilla and two were mandibular lesions. The patients were aged between 2 and 18 years. Treatment ranged from excision and the application of Carnoy's solution to segmental resection and reconstruction. From this case series it can be seen that even in situations where treatment was limited to excision and the application of Carnoy's solution, no recurrences occurred. As such the present authors favour an initially more conservative approach to the management of these lesions where possible and reserving conventional resective treatment for recurrences, lesions causing pathological fracture, and those in regions that are difficult to access.
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