Correlation of EGFR expression, gene copy number and clinicopathological status in NSCLC

Background: Epidermal Growth Factor Receptor (EGFR) targeting therapies are currently of great relevance for the treatment of lung cancer. For this reason, in addition to mutational analysis immunohistochemistry (IHC) of EGFR in lung cancer has been discussed for the decision making of according therapeutic strategies. The aim of this study was to obtain standardization of EGFR-expression methods for the selection of patients who might benefit of EGFR targeting therapies. Methods: As a starting point of a broad investigation, aimed at elucidating the expression of EGFR on different biological levels, four EGFR specific antibodies were analyzed concerning potential differences in expression levels by Immunohistochemistry (IHC) and correlated with fluorescence in situ hybridization (FISH) analysis and clinicopathological data. 206 tumor tissues were analyzed in a tissue microarray format employing immunohistochemistry with four different antibodies including Dako PharmDx kit (clone 2-18C9), clone 31G7, clone 2.1E1 and clone SP84 using three different scoring methods. Protein expression was compared to FISH utilizing two different probes. Results: EGFR protein expression determined by IHC with Dako PharmDx kit, clone 31G7 and clone 2.1E1 (≤ 0.05) correlated significantly with both FISH probes independently of the three scoring methods; best correlation is shown for 31G7 using the scoring method that defined EGFR positivity when ≥ 10% of the tumor cells show membranous staining of moderate and severe intensity (p = 0.001). Conclusion: Overall, our data show differences in EGFR expression determined by IHC, due to the applied antibody. Highest concordance with FISH is shown for antibody clone 31G7, evaluated with score B (p = 0.001). On this account, this antibody clone might by utilized for standard evaluation of EGFR expression by IHC

Reductions in postprandial plasma allantoin concentrations with increasing doses of polyphenol rich curry intake - A randomized crossover trial

10.3389/fphys.2018.01899Frontiers in Physiology10JAN189

Impact of Antimicrobial Usage on Antimicrobial Resistance in Commensal Escherichia coli Strains Colonizing Broiler Chickens

Escherichia coli strains isolated from commercial broilers and an experimental flock of chickens were screened to determine phenotypic expression of antimicrobial resistance and carriage of drug resistance determinants. The goal of this study was to investigate the influence of oxytetracycline, sarafloxacin, and enrofloxacin administration on the distribution of resistance determinants and strain types among intestinal commensal E. coli strains isolated from broiler chickens. We detected a high prevalence of resistance to drugs such as tetracycline (36 to 97%), sulfonamides (50 to 100%), and streptomycin (53 to 100%) in E. coli isolates from treated and untreated flocks. These isolates also had a high prevalence of class 1 integron carriage, and most of them possessed the streptomycin resistance cassette, aadA1. In order to investigate the contribution of E. coli strain distribution to the prevalence of antimicrobial resistance and the resistance determinants, isolates from each flock were DNA fingerprinted by enterobacterial repetitive intergenic consensus sequence (ERIC) PCR. Although very diverse E. coli strain types were detected, four ERIC strain types were present on all of the commercial broiler farms, and two of the strains were also found in the experimental flocks. Each E. coli strain consisted of both susceptible and antimicrobial agent-resistant isolates. In some instances, isolates of the same E. coli strain expressed the same drug resistance patterns although they harbored different tet determinants or streptomycin resistance genes. Therefore, drug resistance patterns could not be explained solely by strain prevalence, indicating that mobile elements contributed significantly to the prevalence of resistance

Disparities in chronic conditions and health status by type of disability

Background Prior research has established health disparities between people with and without disabilities. However, disparities within the disability population, such as those related to type of disability, have been much less studied. Objective To examine differences in chronic conditions and health status between subgroups of people with different types of disability. Methods We analyzed Medical Expenditure Panel Survey annual data files from 2002 to 2008. Logistic regression analyses considered disparity from three perspectives: 1) basic differences, unadjusted for other factors; 2) controlling for key demographic and health covariates; and 3) controlling for a larger set of demographic variables and socioeconomic status as well as health and access to healthcare. Results Individuals with vision, physical, cognitive, or multiple disability types fared worse than people with hearing impairment on most health outcomes. This was most consistently true for people with multiple disabilities. Even when all covariates were accounted for, people with multiple types of disability were significantly more likely (p \u3c 0.05) than those with hearing impairment (reference group) to report every poor health outcome with the exception of BMI ≥ 25 and lung disease. Conclusions While many of the differences between disability types were reduced when controlling for other factors, some differences remained significant. This argues for a more individualized approach to understanding and preventing chronic conditions and poor health in specific disability groups

Use of allostery to identify inhibitors of calmodulin-induced activation of Bacillus anthracis edema factor

Allostery plays a key role in the regulation of the activity and function of many biomolecules. And although many ligands act through allostery, no systematic use is made of it in drug design strategies. Here we describe a procedure for identifying the regions of a protein that can be used to control its activity through allostery. This procedure is based on the construction of a plausible conformational path, which describes protein transition between known active and inactive conformations. The path is calculated by using a framework approach that steers and markedly improves the conjugate peak refinement method. The evolution of conformations along this path was used to identify a putative allosteric site that could regulate activation of Bacillus anthracis adenylyl cyclase toxin (EF) by calmodulin. Conformations of the allosteric site at different steps along the path from the inactive (free) to the active (bound to calmodulin) forms of EF were used to perform virtual screenings and propose candidate EF inhibitors. Several candidates then proved to inhibit calmodulin-induced activation in an in vitro assay. The most potent compound fully inhibited EF at a concentration of 10 μM. The compounds also inhibited the related adenylyl cyclase toxin from Bordetella pertussis (CyaA). The specific homology between the putative allosteric sites in both toxins supports that these pockets are the actual binding sites of the selected inhibitors

Magnetic field therapy enhances muscle mitochondrial bioenergetics and attenuates systemic ceramide levels following ACL reconstruction: Southeast Asian randomized-controlled pilot trial

10.1016/j.jot.2022.09.011Journal of Orthopaedic Translation3599-112complete

Patients with acute and chronic coronary syndromes have elevated long-term thrombin generation

10.1007/s11239-020-02066-yJOURNAL OF THROMBOSIS AND THROMBOLYSIS502421-42