Effect of oxidative stress on ABC transporters: contribution to epilepsy pharmacoresistance

Epilepsy is a neurological disorder affecting around 1%-2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance. The understanding of signalling pathways and mechanism involved may help in identifying potential therapeutic targets and improving drug response

Engineering Education Collaboration: Innovative Pedagogical Methods for High School and University Environmentalists

This paper presents an innovative teaching approach, how it is implemented, student response results of the implementation, and the assessment of impact on student learning. The findings are based on surveys given to the students after each lab lesson taught in partnership with university (Project STEP) and community members. The purpose of this paper is to showcase authentic molecular technology research methods that have been incorporated into a high school level water quality study in cooperation with a watershed restoration program. Typically, water quality studies focus on chemical analysis such as pH, dissolved oxygen, biochemical oxygen demand, orthophosphates, nitrates, temperature, turbidity, macro-invertebrate survey and fecal coliform cultures. This paper shows that by using molecular technology, the source of pollution in the watershed can be determined. Students in these high school science classes are engaged in authentic experiences to identify and analyze human impact on the environment and local ecosystems. Students also are able to collect and analyze data using computer and molecular technology. With help from the local watershed managers, the AP high school students filter bacteria, isolate their DNA, use the polymerase chain reaction (PCR) to amplify the DNA, and finally use gel electrophoresis to trace the DNA to its source (human, cow or intestinal bacteria). In this way, both AP and Physical Science students can extend the water quality study to trace the pollution to a point source. This is a unique approach to high school science laboratory activities. All watershed data is collected and organized using Microsoft Excel spreadsheets and graphing software. Students are able to form conclusions using technology that is used in today\u27s workplace. Initial findings regarding student response to this innovative teaching approach indicate that the actual application of molecular technology methods, employed to solve a problem with an unknown conclusion, is very meaningful to students. Unlike other traditional classroom labs, neither the teacher nor the students know what the results of the watershed tests are before-hand. This type of innovative teaching approach, supported by research on inquiry lessons, provides a more memorable experience for the students - actually performing technology that they would otherwise only read about in textbooks and articles. This paper will provide other instructors with a kind of roadmap, but one where there are experiences of many partners and students that highlight both successes and challenges

Investigating Student Interest in Post-Secondary STEM Education

Interest among students for post-secondary STEM education and causes behind the declining enrollment rate was analyzed. A K-12 survey was developed at the University of Cincinnati to gather information directly from students to verify the teachers\u27 statements regarding K-12 students\u27 perceptions of the engineering profession and studying engineering in college. The K-12 student survey respondents indicated that about 28% of the 6-12 graders were interested in engineering. The survey also showed that students wanted to be an engineer because it was a stable living

Prevalence of Canine Monocytic Ehrlichiosis in Canine Population Across India

Canine ehrlichiosis is a very important emerging disease in India. This study is the first attempt screening a large number of canines in India for the detection of canine monocytic ehrlichiosis. In the present study, 510 blood samples of dogs were screened for the presence of Ehrlichia canis and other variants of Anaplasmataceae family by serological and molecular methods.Out of the 510 serum samples, 293 (57.5%) cases were found positive for the presence of E. canis antibodies through enzyme-linked immunosorbent assay (ELISA). Furthermore, and 45 (8.8%) and 1 (0.2%) specimens were positive for E. canis and A. platys, respectively, based on the polymerase chain reaction (PCR). In the clinical samples of E. canis, the minimum detection limit for PCR was9 ng. In the immunofluorescence assay (IFA), the positive blood samples showed comparable results with those obtained from the commercially available dot ELISA kit (giving equivalent IFA titer). The results of sequencing were compared with other reported isolates in various regions of the world, and a phylogenetic relationship was established. The 16S rRNA region that was amplified and sequenced for E. canis and A. platys was highly conserved and so was another Vir B9 region

Identifying existing Choosing Wisely recommendations of high relevance and importance to hematology

Choosing Wisely (CW) is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. In an effort to learn from and leverage the work of others, the American Society of Hematology CW Task Force developed a method to identify and prioritize CW recommendations from other medical societies of high relevance and importance to patients with blood disorders and their physicians. All 380 CW recommendations were reviewed and assessed for relevance and importance. Relevance was assessed using the MORE TM relevance scale. Importance was assessed with regard to six guiding principles: harm avoidance, evidence, aggregate cost, relevance, frequency and impact. Harm avoidance was considered the most important principle. Ten highly relevant and important recommendations were identified from a variety of professional societies. Recommendations focused on decreasing unnecessary imaging, blood work, treatments and transfusions, as well as on increasing collaboration across disciplines and considering value when recommending treatments. Many CW recommendations have relevance beyond the society of origin. The methods developed by the ASH CW Task Force could be easily adapted by other Societies to identify additional CW recommendations of relevance and importance to their fields. Am. J. Hematol. 91:787–792, 2016. © 2016 Wiley Periodicals, Inc

Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12

PURPOSE: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. PATIENTS AND METHODS: We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life. RESULTS: For the intention-to-treat population, the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, -9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P < .001) and need for hospitalization (P < .001), and preserved quality of life (P = .04). CONCLUSION: For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life

Unmasking the history of 3C 293 with LOFAR sub-arcsecond imaging

Galaxie

First report of multiple lineages of dengue viruses type 1 in Rio de Janeiro, Brazil

<p>Abstract</p> <p>Background</p> <p>In Brazil dengue has been a major public health problem since DENV-1 introduction and spread in 1986. After a low or silent co-circulation, DENV-1 re-emerged in 2009 causing a major epidemic in the country in 2010 and 2011. In this study, the phylogeny of DENV-1 strains isolated in RJ after its first introduction in 1986 and after its emergence in 2009 and 2010 was performed in order to document possible evolutionary patterns or introductions in a re-emergent virus.</p> <p>Findings</p> <p>The analysis of the E gene sequences demonstrated that DENV-1 isolated during 2009/2010 still belong to genotype V (Americas/Africa) but grouping in a distinct clade (lineage II) of that represented by earlier DENV-1 (lineage I). However, strains isolated in 2011 grouped together forming another distinct clade (lineage III).</p> <p>Conclusions</p> <p>The monitoring of DENV is important to observe the spread of potentially virulent strains as well to evaluate its impact over the population during an outbreak. Whether explosive epidemics reported in Brazil caused mainly by DENV-1 was due to lineage replacement, or due the population susceptibility to this serotype which has not circulated for almost a decade or even due to the occurrence of secondary infections in a hyperendemic country, is not clear. This is the first report of multiple lineages of DENV-1 detected in Brazil.</p

Phylogenetic history demonstrates two different lineages of dengue type 1 virus in Colombia

Background: Dengue Fever is one of the most important viral re-emergent diseases affecting about 50 million people around the world especially in tropical and sub-tropical countries. In Colombia, the virus was first detected in the earliest 70′s when the disease became a major public health concern. Since then, all four serotypes of the virus have been reported. Although most of the huge outbreaks reported in this country have involved dengue virus serotype 1 (DENV-1), there are not studies about its origin, genetic diversity and distribution. Results: We used 224 bp corresponding to the carboxyl terminus of envelope (E) gene from 74 Colombian isolates in order to reconstruct phylogenetic relationships and to estimate time divergences. Analyzed DENV-1 Colombian isolates belonged to the formerly defined genotype V. Only one virus isolate was clasified in the genotype I, likely representing a sole introduction that did not spread. The oldest strains were closely related to those detected for the first time in America in 1977 from the Caribbean and were detected for two years until their disappearance about six years later. Around 1987, a split up generated 2 lineages that have been evolving separately, although not major aminoacid changes in the analyzed region were found. Conclusion: DENV-1 has been circulating since 1978 in Colombia. Yet, the phylogenetic relationships between strains isolated along the covered period of time suggests that viral strains detected in some years, although belonging to the same genotype V, have different recent origins corresponding to multiple re-introduction events of viral strains that were circulating in neighbor countries. Viral strains used in the present study did not form a monophyletic group, which is evidence of a polyphyletic origin. We report the rapid spread patterns and high evolution rate of the different DENV-1 lineages