Death of human tumor endothelial cells in vitro through a probable calcium-associated mechanism induced by bevacizumab and detected via a novel method

We isolated three dimensional cell clusters from fresh human solid tumors and also isolated human neoplastic and normal lymphatic cells. Cells were cultured for 96 hours with and without bevacizumab and other agents. At concentrations of bevacizumab which completely removed VEGF from the culture medium, dead microvascular cells were detected through Fast Green/H&E staining as previously described. These peculiar staining characteristics suggested the involvement of calcium, and this was confirmed through staining with Alizarin red S. Using Alizarin staining as a marker for endothelial cell death permitted the use of public domain image analysis software which resulted in a sensitive and specific system for identifying active pharmaceuticals which target the tumor microvasculature at the same time direct antitumor cell effects are determined. Our results suggest an important role for calcium in endothelial cell death mediated by bevacizumab and other agents and further suggest that agents promoting calcium influx may potentiate the activity of antiangiogenic agents

Outpatient antibiotic prescription trends in the United States: A national cohort study

OBJECTIVETo characterize trends in outpatient antibiotic prescriptions in the United StatesDESIGNRetrospective ecological and temporal trend study evaluating outpatient antibiotic prescriptions from 2013 to 2015SETTINGNational administrative claims data from a pharmacy benefits manager PARTICIPANTS. Prescription pharmacy beneficiaries from Express Scripts Holding CompanyMEASUREMENTSAnnual and seasonal percent change in antibiotic prescriptionsRESULTSApproximately 98 million outpatient antibiotic prescriptions were filled by 39 million insurance beneficiaries during the 3-year study period. The most commonly prescribed antibiotics were azithromycin, amoxicillin, amoxicillin/clavulanate, ciprofloxacin, and cephalexin. No significant changes in individual or overall annual antibiotic prescribing rates were found during the study period. Significant seasonal variation was observed, with antibiotics being 42% more likely to be prescribed during February than September (peak-to-trough ratio [PTTR], 1.42; 95% confidence interval [CI], 1.39–1.61). Similar seasonal trends were found for azithromycin (PTTR, 2.46; 95% CI, 2.44–3.47), amoxicillin (PTTR, 1.52; 95% CI, 1.42–1.89), and amoxicillin/clavulanate (PTTR, 1.78; 95% CI, 1.68–2.29).CONCLUSIONSThis study demonstrates that annual national outpatient antibiotic prescribing practices remained unchanged during our study period. Furthermore, seasonal peaks in antibiotics generally used to treat viral upper respiratory tract infections remained unchanged during cold and influenza season. These results suggest that inappropriate prescribing of antibiotics remains widespread, despite the concurrent release of several guideline-based best practices intended to reduce inappropriate antibiotic consumption; however, further research linking national outpatient antibiotic prescriptions to associated medical conditions is needed to confirm these findings.Infect Control Hosp Epidemiol 2018;39:584–589</jats:sec

Smoking, genetic polymorphisms of glutathione S-transferases and biological indices of inflammation and cellular adhesion in the STANISLAS study

A recent clinical study has focused on: 1- the interaction between genetic variants of glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) and smoking on the risk of cardiovascular diseases, 2- the potential capacity of GSTM1 and T1 genotypes in modifying the effect of smoking on inflammation and endothelial function. In this study, we investigated whether carriage of these 2 polymorphisms altered the smoking impact on biological indices of inflammation and cellular adhesion. White blood cell count (WBC), albumin, C-reactive protein (CRP), interleukine-6 (IL-6), tumor necrosis factor-alpha (TNF-a), L-selectin, E-selectin, P-selectin and intracellular adhesion molecule-1 (ICAM-1) were measured in 189 non-smokers and 76 smokers (aged 20-55 years) genotyped for the GSTM1 and T1 polymorphisms. Accounting for age and sex, smokers lacking GSTM1 had a higher WBC count, CRP and ICAM-1 levels as compared to the other groups; interaction term between smoking and genotype being significant (p=0.05). Conversely, non-smokers lacking GSTM1 had a higher levels of TNF-a; the test for interaction being significant (p=0.05). No significant interaction was found between smoking and GSTT1 genotypes, considering the 9 biological indices. However, significantly lower levels of IL-6 were noticed for non-smokers with GSTT1-0 null allele (p=0.05). Our study confirms previous results showing that GSTM1 polymorphism could modulate the interrelationships between smoking and biological markers of inflammation and endothelial function

RESEARCH NOTES AND APPLICATION REPORTS NITROGEN AND FLUORINE DATING OF MOUNDVILLE SKELETAL SAMPLES

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65569/1/j.1475-4754.1982.tb00645.x.pd

Bycatch weight, composition and preliminary estimates of the impact of bycatch reduction devices in Queensland's trawl fishery

This report provides quantitative information on the effects of turtle excluder devices (TEDs) and bycatch reduction devices (BRDs) on the catch rates of bycatch, prawns, scallops and byproduct species, such as Moreton Bay bugs and Balmain bugs, in Queensland’s major trawl fishing sectors. It also provides biological information on, and management advice for several species referred to in the Fishery Management Plan as the permitted species. Several recommendations are included for reducing bycatch in the trawl fishery and for sustaining stocks of the permitted species