Diabetic Foot Screening Tool: Utility in a Busy Primary Care Setting

Abstract Problem: Providers in a Midwest rural clinic identified that foot care is often overlooked due to the complexity of diabetic patients and limited time available during office visits. Purpose: This project examined the utility of an evidence-based, diabetic foot screening tool, provider satisfaction with the tool, and provider perceptions regarding foot care in a busy primary care practice. Methodology: Providers were instructed on using the screening tool. The tool was utilized on all diabetic patients during office visits over a two-month period. Anonymous surveys were distributed and a focus group was conducted to gather post-implementation outcomes. Results: Two providers completed the post-implementation survey and participated in the focus group. Providers were satisfied with the utility of the screening tool. This project resulted in a heightened awareness of the need to perform the recommended foot examinations. Providers also revealed that they would prefer an electronic version of the tool and that they did not agree with one protocol recommendation. Conclusion: Utilizing a screening tool and having clients prepped before the provider entered the room reinforced the need to perform recommended foot examinations. Future projects may include providing an electronic format for the tool and provider education about evidence-based protocol recommendations

MicroRNA-199b-5p Impairs Cancer Stem Cells through Negative Regulation of HES1 in Medulloblastoma

BACKGROUND: Through negative regulation of gene expression, microRNAs (miRNAs) can function in cancers as oncosuppressors, and they can show altered expression in various tumor types. Here we have investigated medulloblastoma tumors (MBs), which arise from an early impairment of developmental processes in the cerebellum, where Notch signaling is involved in many cell-fate-determining stages. MBs occur bimodally, with the peak incidence seen between 3-4 years and 8-9 years of age, although it can also occur in adults. Notch regulates a subset of the MB cells that have stem-cell-like properties and can promote tumor growth. On the basis of this evidence, we hypothesized that miRNAs targeting the Notch pathway can regulated these phenomena, and can be used in anti-cancer therapies. METHODOLOGY/PRINCIPAL FINDINGS: In a screening of MB cell lines, the miRNA miR-199b-5p was seen to be a regulator of the Notch pathway through its targeting of the transcription factor HES1. Down-regulation of HES1 expression by miR-199b-5p negatively regulates the proliferation rate and anchorage-independent growth of MB cells. MiR-199b-5p over-expression blocks expression of several cancer stem-cell genes, impairs the engrafting potential of MB cells in the cerebellum of athymic/nude mice, and of particular interest, decreases the MB stem-cell-like (CD133+) subpopulation of cells. In our analysis of 61 patients with MB, the expression of miR-199b-5p in the non-metastatic cases was significantly higher than in the metastatic cases (P = 0.001). Correlation with survival for these patients with high levels of miR-199b expression showed a positive trend to better overall survival than for the low-expressing patients. These data showing the down-regulation of miR-199b-5p in metastatic MBs suggest a potential silencing mechanism through epigenetic or genetic alterations. Upon induction of de-methylation using 5-aza-deoxycytidine, lower miR-199b-5p expression was seen in a panel of MB cell lines, supported an epigenetic mechanism of regulation. Furthermore, two cell lines (Med8a and UW228) showed significant up-regulation of miR-199b-5p upon treatment. Infection with MB cells in an induced xenograft model in the mouse cerebellum and the use of an adenovirus carrying miR-199b-5p indicate a clinical benefit through this negative influence of miR-199b-5p on tumor growth and on the subset of MB stem-cell-like cells, providing further proof of concept. CONCLUSIONS/SIGNIFICANCE: Despite advances in our understanding of the pathogenesis of MB, one-third of these patients remain incurable and current treatments can significantly damage long-term survivors. Here we show that miR-199b-5p expression correlates with metastasis spread, identifying a new molecular marker for a poor-risk class in patients with MB. We further show that in a xenograft model, MB tumor burden can be reduced, indicating the use of miR199b-5p as an adjuvant therapy after surgery, in combination with radiation and chemotherapy, for the improvement of anti-cancer MB therapies and patient quality of life. To date, this is the first report that expression of a miRNA can deplete the tumor stem cells, indicating an interesting therapeutic approach for the targeting of these cells in brain tumors

Ligand Effects on the Rate and Mechanism of Solvent Exchange at Rhodium(III) and Iridium(III).

The rate constants and activation parameters for solvent exchange for a series of RhIII and IrIII complexes of the form [M(H2O)6]3+ (M = Rh or Ir) and [Cp*M(S)3]2+ (M = Rh or Ir, and S = H2O, MeCN, or Me2SO) have been determined by NMR spectroscopy as a function of free-solvent concentration, temperature, and pressure, and the mechanisms for the respective exchange processes have been inferred

Water jet guided laser as an alternative to EDM for micro-drilling of fuel injector nozzles: A comparison of machined surfaces

To characterize the inner surface of the fuel injector nozzle holes drilled by EDM and water jet guided laser drilling (Laser Micro-Jet) a specifically conceived scanning probe microscopy technique with true non-contact operating mode was used. A difference in morphology of the drilled surfaces is evident from the acquired surface topography along the hole axis for the two compared drilling techniques. Results showed that the surface texture can be characterized by (i) maximum peak-to-valley distance and (ii) periodicity. Acquired maps confirm that electro-eroded surfaces are an envelope of craters randomly distributed with total excursion up to 1.7 μm with a crater size of 15 μm. While, the efficient melt expulsion and immediate cooling of water jet guided laser generates a peak to valley distance of 800 nm with a periodicity of 18 μm. Average Rq derived from the measured cylindrical surfaces was 450 nm and 150 nm for EDM and Laser Micro-Jet, respectively. Water jet guided laser drilling has proved to be a reliable alternative to EDM from the point of view of repeatability of the results and surface quality to facilitate the atomization of the fuel jet

Expression of tert Prevents ALT in Zebrafish Brain Tumors

The activation of a telomere maintenance mechanism (TMM) is an essential step in cancer progression to escape replicative senescence and apoptosis. Alternative lengthening of telomeres (ALT) is found in a subset of malignant brain tumors with poor outcomes. Here, we describe a model of juvenile zebrafish brain tumor that progressively develops ALT. We discovered that reduced expression of tert, linked to a widespread hypomethylation of the tert promoter and increase in Terra expression precedes ALT development. Surprisingly, expression of tert during juvenile brain tumor development led to reduced proliferation of tumor cells and prolonged survival. Most importantly, expression of tert reverted all ALT features and normalizes TERRA expression, promoted heterochromatin formation at telomeres, and attenuated telomeric DNA damage. These data suggest that the activity of telomerase goes beyond telomere maintenance and has profound consequences on genome stability