493 research outputs found

    Foresight w kontekście kultury technicznej

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    The author seeks links between foresight efforts and their social background, particularly culture-related factors which determine how foresight is carried out. Moreover, the article attempts to identify a few risk factors which accompany this type of efforts in connection with the National Foresight Programme Poland 2020.Autor poszukuje związków między próbami wglądu w przyszłość i społecznymi uwarunkowaniami tego rodzaju przedsięwzięć, zwłaszcza czynnikami kulturowymi determinującymi sposób podejmowania takich prób. Ponadto zmierza do wskazania kilku czynników ryzyka towarzyszącego tego rodzaju działalności, wiążących się z Narodowym Programem Foresight „Polska 2020”

    Beck’s Tetrad? Adding POCUS To The Clinical Exam For Pericardial Tamponade Improves Diagnostic Accuracy In Obstructive Shock

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    Beck’s Tetrad? Adding POCUS To The Clinical Exam For Pericardial Tamponade Improves Diagnostic Accuracy In Obstructive Shock Cody Wiench, MD Providence Portland Medical Center – Portland, OR Additional Authors: Benjamin Pedroja, MD Introduction: Obstructive shock due to tamponade is an important, but rare, cause for sudden cardiovascular collapse. Accurate treatment requires prompt (and correct) diagnosis. Bedside echocardiogram can provide rapid and accurate diagnosis, however the physical exam can provide important clues to consider tamponade. In patients with conditions that predispose them to pericardial disease, such as SLE, one must have a high index of suspicion for tamponade when patients suddenly de-compensate. Case Presentation: A 27-year old woman with a history of SLE on chronic immunosuppression, pulmonary hypertension and chronic pain presents to the Emergency Department with subjective fevers to 40C, diaphoresis and sudden onset back pain. Vitals in the ED were impressive for heart rate of 106, blood pressure of 92/67, respiration rate of 10. Labs and imaging were unremarkable. Pt admitted to hospital for potential sepsis of unclear cause in an immunosuppressed patient and was started on vancomycin and piperacillin-tazobactam. On day 5 of hospitalization, a rapid response was called due to sudden onset of heart rate to 150, respiration rate to 24, blood pressures of 80s/50s and severe chest pain. Physical exam at that time was notable for muffled heart sounds and pulsus paradoxus. Bedside ultrasound demonstrated a large pericardial effusion resulting in cardiac tamponade. Emergent pericardial fluid drainage was preformed, draining 70 cc of fibrinous, bloody fluid. After procedure, the patient had rapid normalization of hemodynamics. Pericardial fluid analysis was performed, but nonspecific. It is thought that the effusion was secondary to SLE, and the patient was discharged to home in stable condition. Discussion: Cardiac involvement in SLE is thought to occur in more than 50% of SLE patients, however tamponade is much rarer with an estimated incidence of \u3c1% in a review series. Tamponade portends a poor prognosis in SLE patients. During acute cardiovascular collapse in SLE, one much have a rapid approach to evaluating for tamponade. Pulsus paradoxus is one of those maneuvers; in one prospective study, it was found in 2/3 of patients with tamponade. Unfortunately, patients presenting with the classical “Beck’s Triad” (hypotension, distended neck veins and distant heart sounds) is uncommon; in once study of ultrasound-confirmed tamponade, Beck’s Triad was present in 0% of patients. Fortunately, there are key findings on POCUS exam that, in conjunction with the physical exam, can lead to rapid and accurate diagnosis of tamponade, for instance the absence of a dilated IVC can exclude tamponade with 97% sensitivity.https://digitalcommons.psjhealth.org/ppmc_internal/1006/thumbnail.jp

    Easily Prepared Chiral Scorpionates: Tris(2-oxazolinyl)boratoiridium(I) Compounds and Their Interactions with MeOTf

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    Optically active C3-symmetric monoanionic ligands are uncommon in organometallic chemistry. Here we describe the synthesis of readily prepared tris(4S-isopropyl-2-oxazolinyl)phenylborate [ToP] and fluxional, zwitterionic four- and five-coordinate iridium(I) compounds [Ir(ToP)(η4-C8H12)] (4) and [Ir(ToP)(CO)2] (5). The highly fluxional nature of 4 and5 makes structural assignment difficult, and the interaction between the iridium(I) center and the [ToP] ligand is established by solid-state and solution 15N NMR methods that permit the direct comparison between solution and solid-state structures. Although iridium cyclooctadiene 4 is a mixture of four- and five-coordinate species, the dicarbonyl 5 is only the five-coordinate isomer. The addition of electrophiles MeOTf and MeI provides the oxazoline N-methylated product rather than the iridium methyl oxidative addition product. N-Methylation was unequivocally proven by through-bond coupling observed in 1H−15N HMBC experiments

    Mouse Pxt1 expression is regulated by Mir6996 miRNA

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    Mouse Pxt1 gene is expressed exclusively in male germ cells and encodes for a small, cell death inducing protein. However, upon PXT1 interaction with BAG6, cell death is prevented. In transiently transfected cell lines the PXT1 expression triggered massive cell death, thus we ask the question whether the interaction of PXT1 and BAG6 is the only mechanism preventing normal, developing male germ cells from being killed by PXT1. The Pxt1 gene contains a long 3′UTR thus we have hypothesized that Pxt1 can be regulated by miRNA. We have applied Pxt1 knockout and used Pxt1 transgenic mice that overexpressed this gene to shed more light on Pxt1 regulation. Using the ELISA assay we have demonstrated that PXT1 protein is expressed in adult mouse testis, though at low abundance. The application of dual-Glo luciferase assay and the 3′UTR cloned into p-MIR-Glo plasmid showed that Pxt1 is regulated by miRNA. Combining the use of mirDB and the site-directed mutagenesis further demonstrated that Pxt1 translation is suppressed by Mir6996-3p. Considering previous reports and our current results we propose a model for Pxt1 regulation in the mouse male germ cells

    An in vitro alveolar macrophage assay for predicting the short-term inhalation toxicity of nanomaterials

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    Additional file 1: Table S1. Comparison of significant in vitro LOAECs (significant as compared to the negative benchmark material corundum) to NOAECs and LOAECs recorded in rat STISs. Table S2. Bioactivity of four types of CeO2 NMs in rat STISs as compared to cellular effects recorded in the in vitro NR8383 AM assay

    Cytotoxicity of Elaoephorbia drupifera and other Cameroonian medicinal plants against drug sensitive and multidrug resistant cancer cells

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    BACKGROUND: Multidrug resistance (MDR) is a major hurdle for cancer treatment worldwide and accounts for chemotherapy failure in over 90% of patients with metastatic cancer. Evidence of the cytotoxicity of Cameroonian plants against cancer cell lines including MDR phenotypes is been intensively and progressively provided. The present work was therefore designed to evaluate the cytotoxicity of the methanol extracts of twenty-two Cameroonian medicinal plants against sensitive and MDR cancer cell lines. METHODS: The methanol maceration was used to obtain the crude plant extracts whilst the cytotoxicity of the studied extracts was determined using a resazurin reduction assay. RESULTS: A preliminary assay on leukemia CCRF-CEM cells at 40 μg/mL shows that six of the twenty plant extract were able to enhance less than 50% of the growth proliferation of CCRF-CEM cells. These include Crinum zeylanicum (32.22%), Entada abyssinica (34.67%), Elaoephorbia drupifera (35.05%), Dioscorea bulbifera (45.88%), Eremomastax speciosa (46.07%) and Polistigma thonningii (45.11%). Among these six plants, E. drupifera showed the best activity with IC(50) values below or around 30 μg/mL against the nine tested cancer cell lines. The lowest IC(50) value of 8.40 μg/mL was recorded with the extract of E. drupifera against MDA-MB231 breast cancer cell line. The IC(50) values below 10 μg/mL were recorded with the extracts of E. drupifera against MDA-MB231 breast cancer cells, C. zeylanicum against HCT116 p53(+)/(+) and HCT116p53(-)/(-) colon cancer cells and E. abyssinica against HCT116 p53(+)/(+) cells. CONCLUSION: The results of the present study provide evidence of the cytotoxic potential of some Cameroonian medicinal plants and a baseline information for the potential use of Elaoephorbia drupifera in the treatment of sensitive and drug-resistant cancer cell lines

    Gene expression of metalloproteinase 11, claudin 1 and selected adhesion related genes in papillary thyroid cancer

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    Wstęp: Nadekspresja genów kodujących białka uczestniczące w adhezji komórkowej może być związana z cechami inwazyjności i możliwością przerzutów. Celem pracy było porównanie poziomu ekspresji wybranych genów w rakach brodawkowatych tarczycy (PTC, papillary thyroid carcinoma) w odniesieniu do odpowiadających im tkanek prawidłowych przy użyciu reakcji Q-PCR w czasie rzeczywistym. Materiał i metody: Materiał do badań stanowił całkowity RNA wyizolowany z 38 tkanek raka tarczycy i odpowiadających im tkanek zdrowych. Całkowity RNA w ilości 0,5 μg wykorzystywano w reakcji odwrotnej transkrypcji, z kolei cDNA stanowił matrycę w reakcji Q-PCR. Jako kontrolę wewnętrzną zastosowano gen GUS, którego ekspresja była stabilna we wszystkich analizowanych tkankach. Wyniki: Analizowane geny zostały wytypowane metodą mikromacierzy DNA jako charakterystyczne dla różnicowania PTC od tkanki zdrowej. Poziom ekspresji analizowanych genów, badany poprzez ilościową ocenę odpowiednich transkryptów, był podwyższony w PTC, a jej średnia wartość wynosiła: 1,08 dla CLDN1; 3,98 dla LRP4; 4,57 dla FLRT3; 26,6 dla MRC2; 2,76 dla NRCAM; 0,76 dla MMP11 i 1,35 dla EVA1 w jednostkach arbitralnych, podczas gdy w kontrolnych tkankach zdrowej tarczycy wynosiła odpowiednio: 0,145; 0,7; 0,74; 7,9; 0,85; 0,09; 0,396 jednostek. Dla potwierdzenia ich nadekspresji metodą Q-PCR zastosowano test Kołmogorowa-Smirnowa. Dla wszystkich genów różnice między tkanką prawidłową a PTC były znamienne statystycznie. Wnioski: Spośród badanych genów największe różnice w ekspresji między tkanką PTC a zdrową tkanką tarczycy wykazały geny CLDN1 (klaudyna 1) i MMP11 (metaloproteinaza 11). Gen MMP11 można zaliczyć do grupy charakterystycznej dla nowotworów złośliwych tarczycy, lecz bez wskazania na jego rodzaj, ponieważ istotny wzrost jego ekspresji występuje również w raku rdzeniastym tarczycy. Wydaje się, że gen CLDN1 mógłby być markerem raka brodawkowatego, jednak potrzebna jest weryfikacja przeprowadzonej analizy na dodatkowym materiale.Introduction: Metastasis and invasiveness of thyroid carcinoma might be correlated with over-expression of genes which encode proteins responsible for cellular adhesion. The aim of our study was to compare by means of real-time Q-PCR expression levels of chosen genes in papillary thyroid carcinoma (PTC) with respect to normal thyroid tissues. Material and methods: Total RNA was isolated from 38 paired normal and PTC samples. 0.5 μg of RNA was used in the reverse transcription reaction. cDNA was further used in Q-PCR reaction. As endogenous control we used GUS gene, as its expression was stable in all analysed samples. Results: The analyzed genes were found by microarray studies as characteristic in differentiated papillary carcinoma and normal tissue. The levels of gene expression, estimated by quantitative analysis of particular transcripts were increased in papillary thyroid carcinoma with the following average values: 0.76 for MMP11; 1.08 for CLDN1; 3.98 for LRP4; 4.57 for FLRT3; 26.6 for MRC2; 2.76 for NRCAM; and 1.35 for EVA1 (arbitrary units), whereas in normal thyroid tissues treated as control the respective values were: 0.09; 0.145; 0.7; 0.74; 7.9; 0.85 and 0.396 units. To confirm the overexpression of mentioned genes the conservative Kolmogorov- Smirnov test was used. Differences in expression between normal thyroid tissue and PTC were statistically significant. Conclusions: Among the analyzed genes two show the largest difference in expression between papillary thyroid cancer and normal tissue: MMP11 (metalloproteinase 11) and CLDN1 (claudin 1). The MMP11 gene can be characteristic for various malignant thyroid carcinomas, because its increased levels are present also in medullary thyroid carcinomas. It appears that claudin 1 may be used as a marker of PTC, however a verification on independent collection of tumors of this result is required

    Cytotoxicity and Modes of Action of the Methanol Extracts of Six Cameroonian Medicinal Plants against Multidrug-Resistant Tumor Cells

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    Introduction. The present study aims at evaluating the cytotoxicity of twelve parts from six Cameroonian medicinal plants on sensitive and drug-resistant cancer cell lines. We also studied the mode of action of the most active plants, Gladiolus quartinianus, Vepris soyauxii, and Anonidium mannii. Methods. The cytotoxicity of the extracts was determined using a resazurin assay. Flow cytometry was used for cell-cycle analysis and detection of apoptosis, analysis of mitochondrial membrane potential (MMP), and measurement of reactive oxygen species (ROS). Results. At 40 g/mL, three extracts showed a growth of CCRF-CEM leukemia cells by less than 50%. This includes the extracts from G. quartinianus (GQW; 25.69%), Vepris soyauxii leaves (VSL; 29.82%), and Anonidium mannii leaves (AML; 31.58%). The lowest IC 50 values below 30 g/mL were obtained with GQW, AML and VSL against 7/9, 8/9, and 9/9 tested cancer cell lines, respectively. The lowest IC 50 values for each plant were 4.09 g/mL, and 9.14 g/mL (against U87MG.ΔEGFR cells), respectively, for VSL and AML and 10.57 g/mL (against CCRF-CEM cells) for GQW. GQW induced cell cycle arrest between G0/G1 and S phases, whilst VSL and AML induced arrest in G0/G1. All three extracts induced apoptosis in CCRF-CEM cells by loss of MMP, whilst AML also enhanced production of ROS. Conclusion. The three active plants may be a source for the development of new anticancer drugs

    A multi-gene approach to differentiate papillary thyroid carcinoma from benign lesions: gene selection using support vector machines with bootstrapping

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    Selection of novel molecular markers is an important goal of cancer genomics studies. The aim of our analysis was to apply the multivariate bioinformatical tools to rank the genes – potential markers of papillary thyroid cancer (PTC) according to their diagnostic usefulness. We also assessed the accuracy of benign/malignant classification, based on gene expression profiling, for PTC. We analyzed a 180-array dataset (90 HG-U95A and 90 HG-U133A oligonucleotide arrays), which included a collection of 57 PTCs, 61 benign thyroid tumors, and 62 apparently normal tissues. Gene selection was carried out by the support vector machines method with bootstrapping, which allowed us 1) ranking the genes that were most important for classification quality and appeared most frequently in the classifiers (bootstrap-based feature ranking, BBFR); 2) ranking the samples, and thus detecting cases that were most difficult to classify (bootstrap-based outlier detection). The accuracy of PTC diagnosis was 98.5% for a 20-gene classifier, its 95% confidence interval (CI) was 95.9–100%, with the lower limit of CI exceeding 95% already for five genes. Only 5 of 180 samples (2.8%) were misclassified in more than 10% of bootstrap iterations. We specified 43 genes which are most suitable as molecular markers of PTC, among them some well-known PTC markers (MET, fibronectin 1, dipeptidylpeptidase 4, or adenosine A1 receptor) and potential new ones (UDP-galactose-4-epimerase, cadherin 16, gap junction protein 3, sushi, nidogen, and EGF-like domains 1, inhibitor of DNA binding 3, RUNX1, leiomodin 1, F-box protein 9, and tripartite motif-containing 58). The highest ranking gene, metallophosphoesterase domain-containing protein 2, achieved 96.7% of the maximum BBFR score
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