A retrospective single centre audit on gastric gastrointestinal stromal tumours over a period of fifteen years

Introduction: Gastrointestinal stromal tumours (GIST) are the commonest tumour of mesenchymal origin; favour the stomach, and account for a very small percentage of gastrointestinal tract tumours. Methods: In this retrospective audit of GISTs presenting to the Groote Schuur Hospital surgical and oncological multidisciplinary team (MDT) between 2004 – 2019, gastric GISTs were evaluated as regards presentation, gastric anatomical position, histological subtype with risk stratification, management and outcomes. Results: Of 126 GIST tumours presenting to this MDT, 82 originated in the stomach. Complete histopathological records could be obtained for 64. With an average of 59 years (50 male: 32 female), 18 (28%) presented with a herald bleed. Other common presentations included anaemia, epigastric mass and pain. The tumours were predominantly found in the body and fundus (64%), with a spindle cell subtype predominance (41%). The association between cancer cell subtype and gastric position was not significantly different (p=0.728). Cystic degeneration was found on 11 (17%) analyzed and cell necrosis on 12 (18%). These findings were not related to larger tumor size or prognosis. Five required downstaging with Imatinib prior to surgery. Thirty-seven patients underwent a surgical procedure: 24 wedge resections and 12 anatomical resections. Risk stratification was performed with the modified National Institutes of Health (NIH/Fletcher) score. Twenty-eight cases had inaccurate mitotic counts and couldn't be scored, 17 scored high risk, 9 intermediate risk, 9 low risk and 1 very low risk. Ten patients died of metastatic disease, 34 were discharged with no disease progression after 3 years, 1 patient with disease progression currently remains on Imatinib, and 19 were lost to follow up. Conclusion: Gastric GISTs appear to have a predilection for the proximal stomach; it is unsure whether this is purely due the greater surface area. The spindle cell subtype dominated in the proximal gastric GISTs. Cystic degeneration and cell necrosis did not seem to be related to larger tumours or outcomes

The Process of Parental Bereavement Following the Violent Death of a Child

The purpose of this qualitative study was to explore the process of parental bereavement following the violent death of a child. The death of a child is considered to be the most difficult death anyone can experience which can often result in changing lives forever. Grounded theory was used for this study in an attempt to define the primary concepts contained within the process of parental bereavement when parents lose a child to violent death. Interviews were conducted with 11 parents meeting inclusion criteria. Data collected from the interviews were analyzed using constant comparison and level coding to identify key concepts contained in the process and a framework that revealed the core category of bereavement for these parents as experiencing the process and seeking renewal. The findings revealed a perspective of bereavement as a series of processes which influenced parental bereavement and included positive elements not identified in previous research. The study revealed that the identified categories of telling the story; making critical choices, seeking direction through faith, seeking justice, seeking support, relinquishing the child, and seeking ways of moving forward worked together to facilitate positive outcomes for this high risk and vulnerable population. Support, including family, friends, and religious beliefs, taking an active role in post death activities, and assimilating new roles were other influential elements contained in the process. The concepts that emerged from the data and the resulting framework provide another perspective that can facilitate assessment of parental bereavement behavior. The findings have significance for nursing practice as well as implications for nursing education and research

Multi-Scale Mathematical Modeling of Prion Aggregate Dynamics and Phenotypes in Yeast Colonies

Prion diseases are a multi-scale biological phenomenon that requires understanding intracellular processes as well as how cells interact with each other and their environment. In mammals, prion diseases are progressive, untreatable, and fatal. Yeast prion phenotypes are harmless and reversible, which suggests a deep understanding of the reversal of prion phenotypes in yeast may be informative to mammalian diseases. In yeast, the loss of some prion phenotypes appears to be stochastic and spatially dependent, suggesting a cell-based model of yeast prion dynamics would be a powerful tool for comparisons with experimental results and hypothesis generation. In this work, we consider the components necessary to develop such a model that depicts both the biochemical-, intracellular-, and colony-level scales in yeast prion phenotypes. We first review the literature of mathematical models of the intracellular processes of prion disease. We then review common approaches to cell-based modeling of multicellular systems and how they have led to biological insights in other systems. This chapter ends with a discussion of future studies aimed at motivating how these two types of models can be coupled to produce multi-scale models of prion phenotypes

Human Myoblast and Mesenchymal Stem Cell Interactions Visualized by Videomicroscopy.

Muscle-derived progenitor cell (myoblast) therapy has promise for the treatment of denervated, weakened, and fibrotic muscle. The best methods for injecting myoblasts to promote fusion and retention have yet to be determined, however. Mesenchymal stem/stromal cells have also been reported to have beneficial effects in restoring damaged tissue, through increasing vascularization and reducing inflammation. The interactions between human primary skeletal myoblasts and bone marrow-derived mesenchymal stem/stromal cells were examined using time-lapse images put into video format. Of interest, there is a high degree of cell-to-cell interaction with microparticles transferring between both cell types, and formation of nanotubules to bridge cytoplasmic contents between the two types of cell. This model provides an in vitro platform for examining mechanisms for cell-to-cell interaction preceding myoblast fusion

Destabilization of The Ornithine Decarboxylase mRNA Transcript by the RNA-Binding Protein Tristetraprolin

Ornithine decarboxylase (ODC) is the first and usually rate-limiting enzyme in the polyamine biosynthetic pathway. In a normal physiological state, ODC is tightly regulated. However, during neoplastic transformation, ODC expression becomes upregulated. The studies described here show that the ODC mRNA transcript is destabilized by the RNA-binding protein tristetraprolin (TTP). We show that TTP is able to bind to the ODC mRNA transcript in both non-transformed RIE-1 cells and transformed Ras12V cells. Moreover, using mouse embryonic fibroblast cell lines that are devoid of a functional TTP protein, we demonstrate that in the absence of TTP both ODC mRNA stability and ODC enzyme activity increase when compared to wild-type cells. Finally, we show that the ODC 3′ untranslated region contains cis acting destabilizing elements that are affected by, but not solely dependent on, TTP expression. Together, these data support the hypothesis that TTP plays a role in the post-transcriptional regulation of the ODC mRNA transcript

Tumor Suppressor Activity of ODC Antizyme in MEK-driven Skin Tumorigenesis

To test the hypothesis that suppression of ornithine decarboxylase (ODC) activity blocks the promotion of target cells in the outer root sheath of the hair follicle initiated by Raf/MEK/ERK activation, we crossed mice overexpressing an activated MEK mutant in the skin (K14-MEK mice) with two transgenic lines overexpressing antizyme (AZ), which binds to ODC and targets it for degradation. K14-MEK mice develop spontaneous skin tumors without initiation or promotion. These mice on the ICR background were crossed with K5-AZ and K6-AZ mice on both the carcinogenesis-resistant C57BL/6 background and the sensitive DBA/2 background. Expression of AZ driven by either the K5 or K6 promoter along with K14-MEK dramatically delayed tumor incidence and reduced tumor multiplicity on both backgrounds compared with littermates expressing the MEK transgene alone. The effect was most remarkable in the MEK/K6-AZ mice from the ICR/D2 F1 cross, where double transgenic mice averaged less than one tumor per mouse for more than 8 weeks, while K14-MEK mice averaged over 13 tumors per mouse at this age. Putrescine was decreased in MEK/AZ tumors, while spermidine and spermine levels were unaffected, suggesting that the primary role played by AZ in this system is to inhibit putrescine accumulation. MEK/AZ tumors did not show evidence of apoptosis, but there was a 15–20% decrease in S-phase cells and a 40–60% decrease in mitotic cells in MEK/AZ tumors. These results indicate that the principal effect of AZ may be to slow cell growth primarily by increasing G2/M transit time

Usefulness of the Paralens™ Fluorescent Microscope Adaptor for the Identification of Mycobacteria in Both Field and Laboratory Settings

The presence of acid-fast bacilli (AFB) in laboratories has traditionally been demonstrated using the fluorochrome method, which requires a fluorescent microscope or the Ziehl-Neelsen (ZN) method employing light microscopy. Low sensitivity of the ZN method and high costs of fluoroscopy make the need for a more effective means of diagnosis a top priority, especially in developing countries where the burden of tuberculosis is high. The QBC ParaLens™ attachment (QBC Diagnostic Inc., Port Matilda, PA) is a substitute for conventional fluoroscopy in the identification of AFB. To evaluate the efficacy of the ParaLens LED (light-emitting diode) system, the authors performed a two-part study, looking at usefulness, functionality and durability in urban/rural health clinics around the world, as well as in a controlled state public health laboratory setting. In the field, the ParaLens was durable and functioned well with various power sources and lighting conditions. Results from the state laboratory indicated agreement between standard fluorescent microscopy and fluorescent microscopy using the ParaLens. This adaptor is a welcome addition to laboratories in resource-limited settings as a useful alternative to conventional fluoroscopy for detection of mycobacterial species

Experimental evidence for lamellar magnetism in hemo-ilmenite by polarized neutron scattering

Large local anomalies in the Earth's magnetic field have been observed in Norway, Sweden, and Canada. These anomalies have been attributed to the unusual magnetic properties of naturally occurring hemo-ilmenite, consisting of a paramagnetic ilmenite host (α-Fe2O3-bearing FeTiO3) with exsolution lamellae (≈3μm thick) of canted antiferromagnetic hematite (FeTiO3-bearing α-Fe2O3) and the mutual exsolutions of the same phases on the micron to nanometer scale. The origin of stable natural remanent magnetization (NRM) in this system has been proposed to be uncompensated magnetic moments in the contact layers between the exsolution lamellae. This lamellar magnetism hypothesis is tested here by using polarized neutron diffraction to measure the orientation of hematite spins as a function of an applied magnetic field in a natural single crystal of hemo-ilmenite from South Rogaland, Norway. Polarized neutron diffraction clearly shows that the ilmenite spins do not contribute to the NRM and that hematite spins account for the full magnetization at ambient temperature. Hematite sublattice spins are shown to adopt an average angle of 56∘ with respect to a saturating magnetic field, which is intermediate between the angle of 90∘ predicted for a pure canted moment and the angle of 0∘ predicted for a pure lamellar moment. The observed NRM is consistent with the vector sum of lamellar magnetism and canted antiferromagnetic contributions. The relative importance of the two contributions varies with the length scale of the microstructure, with the lamellar contribution increasing when exsolution occurs predominantly at the nanometer rather than the micrometer scale