22 research outputs found

    Enhancing Visualization Skills-Improving Options aNd Success (EnViSIONS) of Engineering and Technology Students

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    Spatial visualization skills are vital to many careers and in particular to STEM fields. Materials have been developed at Michigan Technological University and Penn State Erie, The Behrend College to assess and develop spatial skills.  The EnViSIONS (Enhancing Visualization Skills-Improving Options aNd Success) project is combining these materials and testing them with pre-college and college students at  seven institutions: Michigan Tech, Penn State Behrend, Purdue University, University of Iowa, Virginia State University, Virginia Tech, and a “Project Lead the Way” course in south-central Arizona.  By removing a barrier to success for students with low visualization skills, particularly women, the project leaders hope to improve the retention of these students in STEM disciplines and to enhance their success. This paper will give a brief overview of the implementations at the university level and the findings

    Neural protection by naturopathic compounds—an example of tetramethylpyrazine from retina to brain

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    Given the advantages of being stable in the ambient environment, being permeable to the blood–brain and/or blood–eye barriers and being convenient for administration, naturopathic compounds have growingly become promising therapeutic candidates for neural protection. Extracted from one of the most common Chinese herbal medicines, tetramethylpyrazine (TMP), also designated as ligustrazine, has been suggested to be neuroprotective in the central nervous system as well as the peripheral nerve network. Although the detailed molecular mechanisms of its efficacy for neural protection are understood limitedly, accumulating evidence suggests that antioxidative stress, antagonism for calcium, and suppression of pro-inflammatory factors contribute significantly to its neuroprotection. In animal studies, systemic administration of TMP (subcutaneous injection, 50 mg/kg) significantly blocked neuronal degeneration in hippocampus as well as the other vulnerable regions in brains of Sprague–Dawley rats following kainate-induced prolonged seizures. Results from us and others also demonstrated potent neuroprotective efficacy of TMP for retinal cells and robust benefits for brain in Alzheimer’s disease or other brain injury. These results suggest a promising prospect for TMP to be used as a treatment of specific neurodegenerative diseases. Given the assessment of the distribution, metabolism, excretion, and toxicity information that is already available on most neuroprotective naturopathic compounds such as TMP, it would not take much preclinical data to justify bringing such therapeutic compounds to clinical trials in humans

    Simple guidelines for efficient referral of soft-tissue sarcomas: a population-based evaluation of adherence to guidelines and referral patterns.

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    BACKGROUND: Optimal treatment of soft-tissue sarcoma requires multidisciplinary management at a sarcoma center. However, these rare tumors are often misinterpreted as benign and many are inadequately treated outside a sarcoma center, with an increased risk of local recurrence that often requires further extensive surgical treatment. To improve referral and centralization of soft-tissue sarcoma management in the southern Sweden health care region, an open-access outpatient clinic at our sarcoma center and simple referral guidelines have been established for the past thirty years. The guidelines call for referral of all deep-seated soft-tissue tumors and of all ≥5-cm superficial tumors before open biopsy or surgery. We evaluated adherence to these guidelines and characterized referral patterns. We also studied the consequences of our strategy with regard to the relative numbers of benign and malignant diagnoses among referred patients. METHODS: Adherence to guidelines, referral pathways, and time to referral to the sarcoma center were analyzed in a population-based series of 100 consecutive patients with soft-tissue sarcoma in the extremities or trunk wall. We also analyzed diagnosis and management of benign and malignant tumors in a second cohort consisting of 464 consecutive patients referred to the sarcoma center because of a soft-tissue tumor. RESULTS: Ninety-seven of the 100 patients with soft-tissue sarcoma were referred to the sarcoma center. All fifty-eight of the deep-seated soft-tissue sarcomas and twenty-eight of the forty-two superficial tumors were referred before open biopsy or surgery. Three-quarters of the patients with soft-tissue sarcoma first presented to a general practitioner. One-quarter of these patients were directly referred to the sarcoma center, which cut the referral time in half compared with patients initially referred to a local hospital. One-quarter of all patients referred to the outpatient clinic were diagnosed with a malignancy, with the majority of the malignancies being soft-tissue sarcoma. CONCLUSIONS: Our simple referral guidelines and open-access outpatient clinic resulted in nearly complete referral of patients with soft-tissue sarcoma to the sarcoma center. The "excess work" associated with referral of benign tumors according to our strategy was limited to the diagnosis of three benign tumors for each malignant tumor. We consider this surplus evaluation of benign tumors acceptable and probably necessary to achieve a high referral rate of soft-tissue sarcoma before initial surgery. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence

    Protein markers for Alzheimer disease in the frontal cortex and cerebellum

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    Objective: To compare proteins related to Alzheimer disease ( AD) in the frontal cortex and cerebellum of subjects with early-onset AD (EOAD) with or without presenilin 1 (PS1) mutations with sporadic late-onset AD ( LOAD) and nondemented control subjects. Methods: Immunohistochemistry, immunoblot analysis, and ELISA were used to detect and assess protein levels in brain. Results: In EOAD and to a lesser extent in LOAD, there was increased amyloid beta (Abeta) deposition (by immunohistochemistry), increased soluble Abeta (by immunoblot analysis), and specific increases in Abeta(40) and Abeta(42) ( by ELISA) in the frontal cortex and, in some cases, in the cerebellum. Surprisingly, immunoblot analysis revealed reduced levels of PS1 in many of the subjects with EOAD with or without PS1 mutations. In those PS1 mutation-bearing subjects with the highest Abeta, PS1 was barely, if at all, detectable. This decrease in PS1 was specific and not attributable solely to neuronal loss because amyloid precursor protein (APP) and the PS1-interacting protein beta-catenin levels were unchanged. Conclusions: This study shows that in the frontal cortex and cerebellum from Alzheimer disease patients harboring certain presenilin 1 mutations, high levels of amyloid beta are associated with low levels of presenilin 1. The study provides the premise for further investigation of mechanisms underlying the downregulation of presenilin 1, which may have considerable pathogenic and therapeutic relevance

    Can enzyme kinetics of prooxidants teach us a lesson about the treatment of Alzheimer's disease: a pilot post-mortem study

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    OBJECTIVES: Oxidative stress (OS), is defined as an imbalance of pro- and antioxidants, leading to increased production of free radicals, which can lead to cell damage and death, has been postulated as important factors in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Most research has concentrated on the antioxidant system, for the first time, this proof of concept study examines the prooxidant system by investigating kinetic parameters of the free radical producing enzyme xanthine oxidase directly in post mortem brain tissue. METHODS: We determined the Michaelis-Menten constant (K(M)) and the maximal velocity (V(Max)) of xanthine oxidase (XO) in the cortico-limbic system of patients with AD using activity assays. RESULTS: We found the Michaelis-Menton constant of XO significantly decreased in hippocampus of patients with AD compared to controls. None of the other brain regions showed any significant alterations of these parameters. CONCLUSIONS: These results add further evidence to the amount of research indicating that OS plays an important role in AD. Moreover, these results should encourage more research in this field and it maybe speculated that this might open new avenues for treatment and prevention in AD

    Heterogenous mismatch-repair status in colorectal cancer

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    Background: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. Methods: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative expression patterns macro-dissected and micro-dissected tumor areas were separately analyzed for microsatellite instability and MLH1 promoter methylation. Results: Heterogenous retained/lost mismatch repair protein expression could be classified as intraglandular (within or in-between glandular formations), clonal (in whole glands or groups of glands) and compartmental (in larger tumor areas/compartments or in between different tumor blocks). These patterns coexisted in 9/14 tumors and in the majority of the tumors correlated with differences in microsatellite instability/MLH1 methylation status. Conclusions: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/177194032312678
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