Characterization of oxidative stress in Leishmaniasis-infected or LPS-stimulated macrophages using electrochemical impedance spectroscopy

The physiological changes caused by external stimuli can be employed as parameters to study pathogen infection in cells and the effect of drugs. Among analytical methods, impedance is potentially useful to give insight into cellular behavior by studying morphological changes, alterations in the physiological state, production of charged or redox species without interfering with in vitro cellular metabolism and labeling. The present work describes the use of electrochemical impedances spectroscopy to simply monitor by modeling impedance plots (Nyquist diagram) in appropriate equivalent circuit, the changes affecting murine macrophage cell line (RAW 264.7) in response to parasite infection by Leishmania amazonensis or to lipopolysaccharide (LPS) treatment. These results demonstrate the ability of electrochemical impedance spectroscopy to discriminate between two opposite cell responses associated to two different stimuli, one caused by the internalization of a parasite, and the other by activation by a bacterium component. Indeed, the study has allowed the characterization, from an electrical point of view, of the extra-cellular NO radical produced endogenously and in great quantities by the inducible form of NO-synthase in the case of LPS-stimulatedmacrophages. This production was not observed in the case of Leishmania-infectedmacrophages for which to survive and multiply, the parasite itself possesses mechanisms which may interfere with NO production. In this latest case, only the intracellular production of ROS was observed. To confirm these interpretations confocal microscopy analysis using the ROS (reactive oxygen species) fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate and electron paramagnetic resonance experiments using Fe(DETC)2 as NO radical spin trap were carried out

Synchronous gastric and duodenal metastases from head and neck squamous cell carcinoma: a unique presentation of upper gastrointestinal bleeding.

Metastatic disease to the stomach or duodenum is an infrequent diagnosis, and head and neck squamous cell carcinoma (HNSCC) is one of the least common primary malignancies that lead to gastric or duodenal metastases. We report the case of a 65-year-old man with human immunodeficiency virus infection and previously diagnosed HNSCC who presented with melena. The patient had a percutaneous endoscopic gastrostomy tube placed 3 months prior to his presentation. Laboratory testing was significant for normocytic anemia and a digital rectal examination was positive for melena. Esophagogastroduodenoscopy revealed numerous cratered nodules with contact bleeding in the stomach as well as the duodenum that appeared malignant. Biopsies of the gastric and duodenal nodules were positive for p40 and CK 5/6, consistent with metastatic squamous cell carcinoma

Deregulated expression of aurora kinases is not a prognostic biomarker in papillary thyroid cancer patients.

Abstract A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, butno information regarding its possible prognostic role in differentiated thyroid cancer is available. Here, weevaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up-or down-regulatedin the majority of cancer tissues. In particular, Aurora-A and Aurora-B mRNA levels were altered, respectively, in 55 (63.2%) and 79 (90.8%) out of the 87 PTC analyzed. A significant positive correlation between Aurora-A and Aurora-B mRNAswas observed (p=0.001). The expression of both Aurora genes was not affected by the BRAF(V600E) mutation. Univariate, multivariate and Kaplan-Mayer analyses documented the lack of association between Aurora-A or Aurora-B expression and clinicopathological parameterssuch as gender, age, tumor size, histology, TNM stage, lymph node metastasis and BRAF status as well asdisease recurrences or disease-free interval. Only Aurora-B mRNA was significantly higher in T(3-4) tissues, with respect to T(1-2) PTC tissues. The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker inPTC patients

A novel integrative risk index of papillary thyroid cancer progression combining genomic alterations and clinical factors.

Although the majority of papillary thyroid cancer (PTC) is indolent, a subset of PTC behaves aggressively despite the best available treatment. A major clinical challenge is to reliably distinguish early on between those patients who need aggressive treatment from those who do not. Using a large cohort of PTC samples obtained from The Cancer Genome Atlas (TCGA), we analyzed the association between disease progression and multiple forms of genomic data, such as transcriptome, somatic mutations, and somatic copy number alterations, and found that genes related to FOXM1 signaling pathway were significantly associated with PTC progression. Integrative genomic modeling was performed, controlling for demographic and clinical characteristics, which included patient age, gender, TNM stages, histological subtypes, and history of other malignancy, using a leave-one-out elastic net model and 10-fold cross validation. For each subject, the model from the remaining subjects was used to determine the risk index, defined as a linear combination of the clinical and genomic variables from the elastic net model, and the stability of the risk index distribution was assessed through 2,000 bootstrap resampling. We developed a novel approach to combine genomic alterations and patient-related clinical factors that delineates the subset of patients who have more aggressive disease from those whose tumors are indolent and likely will require less aggressive treatment and surveillance (p = 4.62 × 10-10, log-rank test). Our results suggest that risk index modeling that combines genomic alterations with current staging systems provides an opportunity for more effective anticipation of disease prognosis and therefore enhanced precision management of PTC

From Burdens To Benefits: The Societal Impact Of PDL-Enriched, Efficacy-Enhanced Educators

Societies continue to absorb increased burdens in cost for helping citizens unable to achieve at optimal levels.  Building on past research, we project educational benefits to offset current societal burdens through enhanced educator capabilities.  Studies reviewed show participation in a high-impact professional development and learning solution resulted in improved student performance and reduced dropout rates, reduced disciplinary rates and increased rates for college-bound, along with lower teacher turnover.  Computations show that generalization of such impacts should trade societal burdens for benefits at between $3.7 billion and$6.9 billion within the first year.  Cumulatively within 20 years the burdens converted to benefits are projected to exceed $85 billion.  Enhanced educator capabilities will substantively reduce needs and costs for societal programs, replaced with tangible benefits to all

More Sound-Spelling Correspondences

This article is a sequel to Sound-Spelling Correspondences in the May 1985 Word Ways, providing additional spellings for the indicated pronunciations. All have been taken from Webster\u27s Third Edition

Sustaining Student Gains From Online On-Demand Professional Development

A multi-State, quasi-experimental study was conducted as a longitudinal, two-year follow-up of participation in an online, on-demand professional development (PD) program.  The purpose was to ascertain whether student gains were sustained in a second year of PD participation.  Data verified gains in Year 1 versus Pre-PD baseline, with continued gains in Year 2 atop those achieved in year 1 of PD participation, reflecting a positive trend and continued advantage over non-PD schools in the same districts.  Results showed that student in PD schools gained 7.7% (p<.01) more in Math in year 2 atop 18.9% (p<.001) gains from year 1, versus gains of 0.5% (ns) and 4.2% (p<.01) for non-PD schools in the same districts.  Similarly, students in the PD schools gained 10.2% (p<.01) more in Reading in year 2 atop 18.9% (p<.001) gains from year 1, versus gains of 0.5% (ns) and 4.2% (p<.01) for non-PD schools in the same districts.  Total gains from baseline for PD schools were 28.1% (p<0.001) in Math for PD schools versus 4.7% (p<0.01) for the same districts collectively, and 30.2% (p<0.001) in Reading for PD schools versus 6.0% (p<0.01) for the same districts collectively.  Findings support the high-participation use of Internet-based, on-demand professional learning for improving teacher effectiveness and sustained impacts on student performance

Control charts for health care monitoring: the heterogeneous case

Attribute data from high quality processes can be monitored adequately by using negative binomial charts. The optimal choice for the number r of failures involved depends on the expected rate of change in failure rate during Out-of-Control. To begin with, such results have been obtained for the case of homogeneous data. But especially in health care monitoring, (groups of) patients will often show large heterogeneity. In the present paper we will present an overview of how this problem can be dealt with. Two situations occur: the underlying structure is either unknown (the overdispersion case) or known (risk adjustment feasible). An additional complication to be dealt with is the fact that in practice typically all parameters involved are unknown. Hence estimated versions of the new proposals need to be discussed as well

Improved binomial charts for high-quality processes

For processes concerning attribute data with (very) small failure rate p, often negative binomial control charts are used. The decision whether to stop or continue is made each time r failures have occurred, for some r≥1. Finding the optimal r for detecting a given increase of p first requires alignment of the charts in terms of in-control behavior. In the present paper binomial charts are subjected to this same requirement. Subsequent study reveals that the resulting charts are quite attractive in several aspects, such as detection power. For the case of unknown p, an estimated version of the chart is derived and studied