Low Bone Turnover in Chronic Kidney Disease is associated with decreased VEGF-A expression and osteoblast differentiation

Background: Low turnover bone (low bone formation rates (BFRs)) with decreased osteoblast number is common in patients with chronic kidney disease (CKD) and attributed to ‘over-suppression' of the parathyroid hormone (PTH) despite supra-physiologic levels. An alternative hypothesis is abnormal osteoblast differentiation, resulting in low BFRs due to reduced VEGF-A. Methods: We analyzed the expression of VEGF-A and mesenchymal stem cell (MSC) differentiation factors in freshly isolated bone marrow (BM) cells, and in BM cell-derived MSC in rats with different levels of BFRs and PTH (modulated by calcium and zoledronic acid). The regulators of VEGF in MSC were also determined. Results: VEGF-A expression was reduced in the BM cells from CKD vs. normal animals (p < 0.02). In BM-derived MSC from CKD, there were decreased osteoblast transcription factors and mineralization. In CKD animals, the BM VEGF-A expression was positively correlated with BFR (r = 0.80, p < 0.001). Reducing BFRs in CKD animals led to reductions in VEGF-A expression and osteoblast transcription factors regardless of the PTH level. We therefore examined other regulators of VEGF-A and found decreased expression of hypoxia-inducible factor-1α and the master transcription factor of antioxidants nuclear factor (erythroid-derived 2)-like 2 in CKD animals with low PTH. Conclusion: Low BFRs in CKD are associated with a basal decrease in VEGF-A expression in BM that may be driven by altered hypoxia and oxidative stress

The Role of Surgery, Radiosurgery and Whole Brain Radiation Therapy in the Management of Patients with Metastatic Brain Tumors

Brain tumors constitute the most common intracranial tumor. Management of brain metastases has become increasingly complex as patients with brain metastases are living longer and more treatment options develop. The goal of this paper is to review the role of stereotactic radiosurgery (SRS), whole brain radiation therapy (WBRT), and surgery, in isolation and in combination, in the contemporary treatment of brain metastases. Surgery and SRS both offer management options that may help to optimize therapy in selected patients. WBRT is another option but can lead to late toxicity and suboptimal local control in longer term survivors. Improved prognostic indices will be critical for selecting the best therapies. Further prospective trials are necessary to continue to elucidate factors that will help triage patients to the proper brain-directed therapy for their cancer

First-Generation College Students at the University of Kentucky

First-generation college students (FGCS) have been shown to graduate at lower rates than their continuing-generation counterparts even after controlling for other variables. We will attempt to examine the characteristics of FGCS and determine initiatives the University of Kentucky might enact in order to increase the graduation rates for this segment of the student population. In doing so we will discuss “promising practices” in student retention, examine programs designated by UK’s Top-20 plan as benchmark institutions, and submit a series of recommendations to better serve FGCS at the University of Kentucky

Determining patient and primary care delay in the diagnosis of cancer – lessons from a pilot study of patients referred for suspected cancer

<p>Abstract</p> <p>Background</p> <p>There is no validated way of measuring diagnostic delay in cancer, especially covering patient and primary care delays. An instrument is needed in order to determine the effect of potential interventions to reduce delay and improve cancer morbidity and mortality.</p> <p>Methods</p> <p>Development of a postal questionnaire tool to measure patient and primary care time responses to key symptoms and signs. The pilot questionnaire was sent to 184 patients with suspected cancer.</p> <p>Results</p> <p>The response rate was only 85/184 (46.2%). Anxiety was cited as one reason for this low response. Patients returning questionnaires were more likely to be women and more likely to be younger. 84/85 (98.8%) provided consent to access medical records, and questions regarding health profile, smoking and socio-economic profile were answered adequately. Outcome data on their cancer diagnosis was linked satisfactorily and the question about GP-initiated investigations was answered well. Estimated dates for symptom duration were preferred for patient delays, but exact dates were preferred for primary care delays; however there was a significant amount of missing data.</p> <p>Conclusion</p> <p>A more personal approach to the collection of data about the duration of symptoms in this group of people is needed other than a postal questionnaire. However elements of this piloted questionnaire are likely to figure strongly in future development and evaluation of this tool.</p

Constraining the structure of the non-spherical preprotostellar core L1544

A series of self-consistent, three-dimensional continuum radiative transfer models are constructed of the pre-protostellar core L1544, with the results compared with existing SCUBA and ISO data. The source is well-fit by a prolate spheroid, having an ellipsoidal power-law density distribution of index m ~ 2 (1.75 < m < 2.25) in to at least r ~ 1600AU. For r<1600 AU, the data are consistent with either an extension of the power law to smaller radii, or a flattened (Bonner-Ebert like) density distribtion. We can further constrain the optical depth along the short axis at 1300um to be ~ 5e-3, the central luminosity to be L < 1e-3 solar luminosities, the long axis diameter D ~ 0.1 pc, the axis ratio to be q ~ 2, and the external ISRF to be similar to that defined by Mathis, Mezger, & Panagia (1983) to within 50 per cent. The outer diameter and axis ratio may each be somewhat larger due to potential on-source chopping in the observations, and the projection of the long axis onto the plane of the sky. While these results are similar to those inferred directly from observations or spherical modeling due to the source transparency at submillimeter wavelengths, we infer a smaller size, lower mass, and higher optical depth / column density, exposed to a stronger external radiation field than previously assumed. Finally, we find that both the spectral energy distribution (SED) and surface brightness distribution are necessary to constrain the source properties in this way.Comment: 9 pages; 8 figures; accepted for publication in MNRA

SynthoPlate: A platelet-inspired hemostatic nanotechnology for treatment of bleeding complications

Platelet transfusions are routinely used in the clinic to treat bleeding complications stemming from trauma, surgery, malignancy-related bone marrow dysfunctions, and congenital or drug-related defects platelet defects. These transfusions primarily use allogeneic platelet concentrates (PCs) that pose issues of limited availability and portability, high risk of bacterial contamination, very short shelf life (~3-5 days), need for antigen matching and several biologic side effects. While robust research is being directed at resolving some of these issues, there is in parallel a significant clinical interest in synthetic platelet substitutes that can render efficient hemostasis by leveraging and amplifying endogenous clotting mechanisms while avoiding the above issues. To this end, we have developed a unique platelet-inspired synthetic hemostat technology called the SynthoPlate® (US Patent 9107845). Since platelets promote primary hemostasis via adhesion to vWF and collagen at the injury site and concomitant aggregation via fibrinogen binding to integrin GPIIb-IIIa on active platelets, we have mimicked and integrated these key hemostatic mechanisms on the SynthoPlate® by heteromultivalent surface-engineering of a liposomal platform with vWF-binding peptides (VBP), collagen-binding peptides (CBP) and fibrinogen-mimetic peptides (FMP). These ~150nm diameter SynthoPlate® vesicles are sterilizable and can be stored as lyophilized powder for long periods of time. We demonstrated, in vitro, that this platelet-mimetic integrative design renders hemostatically relevant functions at levels significantly higher than designs that mimic platelet’s adhesion function only or aggregation function only. We further demonstrated in vitro that SynthoPlate®-mediated site-selective amplification of primary hemostatic mechanisms (active platelet recruitment and aggregation) in effect results in site-selective enhancement of secondary hemostatic function (fibrin generation). We also established that SynthoPlate® does not activate and aggregate resting platelets or trigger coagulation mechanisms in plasma, suggesting that this technology will not have systemic pro-thrombotic and coagulatory risks. The hemostatic efficacy of SynthoPlate® was tested in appropriate tail-transection and liver bleeding models in mice, as well as, pilot studies in arterial bleeding model in pigs. In tail-transection bleeding model in normal as well as thrombocytopenic mice, prophylactically administered SynthoPlate® was able to significantly reduce bleeding time by 60-70%. In laparotomy traumatic bleeding model in mice, prophylactically administered SynthoPlate® was able to reduce blood volume loss by ~30%, reduced hypotension effects and increased survival by \u3e80%. In pilot pig models of arterial bleeding, emergency administration of SynthoPlate® has shown substantial reduction in blood volume loss. Immunohistological evaluation of tissues from various treated animals have shown marked co-localization of red fluorescent SynthoPlate® with green fluorescent platelets localized at the clot site. Biodistribution studies in animals indicate that SynthoPlate® is cleared primarily by liver and spleen, similar to clinically known liposomal technologies. We have also demonstrated that the platelet-mimetic heteromultivalent surface-decoration approach can be adapted to other biomedically relevant particle platforms. Altogether, our studies establish the promise of SynthoPlate® nanotechnology as a platelet-mimetic intravenous hemostat for treatment of bleeding complications in prophylactic and emergency scenarios. Ongoing studies are focused on evaluating this technology in clinically motivated large animal bleeding models, with a vision for translation

Transcriptional responses of Arabidopsis thaliana plants to As (V) stress

Background Arsenic is toxic to plants and a common environmental pollutant. There is a strong chemical similarity between arsenate [As (V)] and phosphate (Pi). Whole genome oligonucleotide microarrays were employed to investigate the transcriptional responses of Arabidopsis thaliana plants to As (V) stress. Results Antioxidant-related genes (i.e. coding for superoxide dismutases and peroxidases) play prominent roles in response to arsenate. The microarray experiment revealed induction of chloroplast Cu/Zn superoxide dismutase (SOD) (at2g28190), Cu/Zn SOD (at1g08830), as well as an SOD copper chaperone (at1g12520). On the other hand, Fe SODs were strongly repressed in response to As (V) stress. Non-parametric rank product statistics were used to detect differentially expressed genes. Arsenate stress resulted in the repression of numerous genes known to be induced by phosphate starvation. These observations were confirmed with qRT-PCR and SOD activity assays. Conclusion Microarray data suggest that As (V) induces genes involved in response to oxidative stress and represses transcription of genes induced by phosphate starvation. This study implicates As (V) as a phosphate mimic in the cell by repressing genes normally induced when available phosphate is scarce. Most importantly, these data reveal that arsenate stress affects the expression of several genes with little or unknown biological functions, thereby providing new putative gene targets for future research

Deep learning optimized single-pixel LiDAR

Interest in autonomous transport has led to a demand for 3D imaging technologies capable of resolving fine details at long range. Light detection and ranging (LiDAR) systems have become a key technology in this area, with depth information typically gained through time-of-flight photon-counting measurements of a scanned laser spot. Single-pixel imaging methods offer an alternative approach to spot-scanning, which allows a choice of sampling basis. In this work, we present a prototype LiDAR system, which compressively samples the scene using a deep learning optimized sampling basis and reconstruction algorithms. We demonstrate that this approach improves scene reconstruction quality compared to an orthogonal sampling method, with reflectivity and depth accuracy improvements of 57% and 16%, respectively, for one frame per second acquisition rates. This method may pave the way for improved scan-free LiDAR systems for driverless cars and for fully optimized sampling to decision-making pipelines

VirMAP for Cancer: Characterization of the Intratumoral Virome in Virally-Associated Cancers and a Resource for Investigators

View full abstracthttps://openworks.mdanderson.org/leading-edge/1040/thumbnail.jp