Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database

Objective To determine the extent to which antibiotics reduce the risk of serious complications after common respiratory tract infections.Design Retrospective cohort study.Setting UK primary care practices contributing to the general practice research database.Data source 3.36 million episodes of respiratory tract infection.Main outcome measures Risk of serious complications in treated and untreated patients in the month after diagnosis: mastoiditis after otitis media, quinsy after sore throat, and pneumonia after upper respiratory tract infection and chest infection. Number of patients needed to treat to prevent one complication.Results Serious complications were rare after upper respiratory tract infections, sore throat, and otitis media, and the number needed to treat was over 4000. The risk of pneumonia after chest infection was high, particularly in elderly people, and was substantially reduced by antibiotic use, with a number needed to treat of 39 for those aged ≥65 and 96-119 in younger age groups. Conclusion Antibiotics are not justified to reduce the risk of serious complications for upper respiratory tract infection, sore throat, or otitis media. Antibiotics substantially reduce the risk of pneumonia after chest infection, particularly in elderly people in whom the risk is highest.     

3-Mercaptopropionic acids as efficacious inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa)

A novel series of cyclic potent, selective, small molecule, thiol-based inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa) and the crystal structures of TAFIa inhibitors bound to porcine pancreatic carboxypeptidase B are described. Three series of cyclic arginine and lysine mimetic inhibitors vary significantly in their selectivity against other human basic carboxypeptidases, carboxypeptidase N and carboxypeptidase B. (-)2a displays TAFIa IC50 = 3 nM and 600-fold selectivity against CPN. Inhibition of TAFIa with (rac)2a resulted in dose dependent acceleration of human plasma clot lysis in vitro and was efficacious as an adjunct to tPA in an in vivo rabbit jugular vein thrombolysis model.     

Breeding Potential of Some Exotic Tomato Lines: A Combined Study of Morphological Variability,Genetic Divergence,and Association of Traits

Tomato (Solanum lycopersicum L.) is called ‘the poor man’s orange’ due to its low price and improved nutritional values. An experiment was conducted to study the breeding potential of some exotic tomato lines by assessing various qualitative and quantitative traits conferring yield and quality attributes. Among the qualitative traits, greater variability was observed for growth type, stem hairiness, and fruit shape and size. A determinate growth habit was observed in the genotype AVTO9802 while the genotype AVTO0102 produced yellow color fruits. A significant (p ≤ 0.01) variation was also observed for the studied quantitative traits. Based on yield and traits attributed to yield, the genotypes AVTO0314, GPB0107, GPB0120 and AVTO9802 were selected as promising genotypes. The differences between the genotypic and phenotypic coefficients of variation (GCV and PCV) of the studied quantitative traits were very low. This suggests that the apparent variation was mainly due to the genotypes. The higher GCV and PCV values were observed for the number of primary branches plant⁻¹ (NPB), number of fruits cluster⁻¹ (NFC), individual fruit weight (IFW) and total soluble solids (TSS). High heritability was recorded for all quantitative traits in a broad sense. However, the individual fruit diameter showed the highest heritability (99.56). The highest (102.75) genetic advance (GA) was observed for the number of fruits plant⁻¹ (NFP). High heritability coupled with high GA as percentage of mean were recorded for the traits NFP, NFC, fruit yield plant⁻¹ (FYP) and IFW. FYP showed a significant positive correlation with NFC (0.714***) and a negative correlation with days to the first harvest (−0.539***) and plant height (−0.492**). Principal component analysis revealed that the first four components explained 78.5% of the total variation among the genotypes. Thus, the promising genotypes (AVTO0314, GPB0107, GPB0120, AVTO9802 and AVTO0102) isolated from this study can be used for developing high-yielding and high-quality tomato varieties.     

SHANK3 genetic polymorphism and susceptibility to ASD: evidence from molecular,in silico,and meta-analysis approaches

Molecular Biology Reports - The SHANK3 gene encodes a master synaptic scaffolding protein at the excitatory synapse’s postsynaptic density, which is predominantly responsible for constructing...     

Rewired Metabolism in Drug-resistant Leukemia Cells: A METABOLIC SWITCH HALLMARKED BY REDUCED DEPENDENCE ON EXOGENOUS GLUTAMINE*

Cancer cells that escape induction therapy are a major cause of relapse. Understanding metabolic alterations associated with drug resistance opens up unexplored opportunities for the development of new therapeutic strategies. Here, we applied a broad spectrum of technologies including RNA sequencing, global untargeted metabolomics, and stable isotope labeling mass spectrometry to identify metabolic changes in P-glycoprotein overexpressing T-cell acute lymphoblastic leukemia (ALL) cells, which escaped a therapeutically relevant daunorubicin treatment. We show that compared with sensitive ALL cells, resistant leukemia cells possess a fundamentally rewired central metabolism characterized by reduced dependence on glutamine despite a lack of expression of glutamate-ammonia ligase (GLUL), a higher demand for glucose and an altered rate of fatty acid β-oxidation, accompanied by a decreased pantothenic acid uptake capacity. We experimentally validate our findings by selectively targeting components of this metabolic switch, using approved drugs and starvation approaches followed by cell viability analyses in both the ALL cells and in an acute myeloid leukemia (AML) sensitive/resistant cell line pair. We demonstrate how comparative metabolomics and RNA expression profiling of drug-sensitive and -resistant cells expose targetable metabolic changes and potential resistance markers. Our results show that drug resistance is associated with significant metabolic costs in cancer cells, which could be exploited using new therapeutic strategies.     

ADSBET2: Automated Determination of Salt-Bridge Energy-Terms version 2

AvailabilityADSBET2 is freely available at http://sourceforge.net/projects/ADSBET2/ for all users.