Host Antimicrobial Peptides: the promise of new treatment strategies against Tuberculosis

Tuberculosis (TB) continues to be a devastating infectious disease and remerges as a global health emergency due to an alarming rise of antimicrobial resistance to its treatment. Despite of the serious effort that has been applied to develop effective antitubercular chemotherapies, the potential of antimicrobial peptides (AMPs) remains underexploited. A large amount of literature is now accessible on the AMP mechanisms of action against a diversity of pathogens; nevertheless, research on their activity on mycobacteria is still scarce. In particular, there is an urgent need to integrate all available interdisciplinary strategies to eradicate extensively drug-resistant Mycobacterium tuberculosis strains. In this context, we should not underestimate our endogenous antimicrobial proteins and peptides as ancient players of the human host defense system. We are confident that novel antibiotics based on human AMPs displaying a rapid and multifaceted mechanism, with reduced toxicity, should significantly contribute to reverse the tide of antimycobacterial drug resistance. In this review, we have provided an up to date perspective of the current research on AMPs to be applied in the fight against TB. A better understanding on the mechanisms of action of human endogenous peptides should ensure the basis for the best guided design of novel antitubercular chemotherapeutics

Second-generation antipsychotic effect on cognition in patients with schizophrenia : a meta-analysis of randomized clinical trials

Objective To investigate the effect of second-generation antipsychotics on cognitive function in patients diagnosed with schizophrenia or schizoaffective disorder. Method Multiple-treatments meta-analysis model. Results On cognitive composite score, sertindole was superior to clozapine, effect size (ES) 0.87; 95% CI: 0.12–1.63, quetiapine, ES 0.75; 95% CI: 0.00–1.49, and first-generation antipsychotics (FGAs), ES 0.89; 95% CI: 0.14–1.64. Analyses on each cognitive domain showed clozapine, ES 0.37; 95% CI: 0.00–0.74, olanzapine, ES 0.31; 95%CI: 0.02–0.59, quetiapine, ES 0.34; 95% CI: 0.03–0.64, and FGAs, ES 0.51; 95% CI: 0.18–0.83 performing poorer on verbal working memory than ziprasidone, as well as FGAs performing poorer than risperidone, ES 0.31; 95% CI: 0.04–0.58. On executive function, sertindole performed better than clozapine, ES 0.82; 95% CI: 0.06–1.58, olanzapine, ES 0.81; 95% CI: 0.07–1.55, quetiapine, ES 0.76; 95% CI: 0.02–1.51, ziprasidone, ES 0.90; 95% CI: 0.14–1.67, and FGAs, ES 0.83; 95% CI: 0.08–1.58. On processing speed, FGAs performed poorer than sertindole, ES 0.97; 95% CI: 0.02–1.91, and quetiapine, ES 0.36; 95% CI: 0.01–0.72. On long-term verbal working memory, clozapine performed poorer than olanzapine, ES 0.41; 95% CI: 0.06–0.76. On verbal fluency, FGAs performed poorer than olanzapine, ES 0.26; 95% CI: 0.01–0.50, and clozapine, ES 0.44; 95% CI: 0.06–0.81. Lastly, FGAs, ES 0.41; 95% CI: 0.04–0.78, and clozapine, ES 0.44; 95% CI: 0.05–0.83, performed poorer on visuospatial skill compared to olanzapine. Conclusion The meta-analysis was able to detect some trends in the data analyzed, but did not show any drug having a uniform positive cognitive profile

Hydrogen sorption in TiZrNbHfTa high entropy alloy

© 2018 Elsevier B.V. High Entropy Alloys (HEA), where five or more elements are mixed together in near equiatomic ratios offer promising properties as hydrogen storage materials due to their ability to crystallize in simple cubic structures in the presence of large lattice strain originating from the different sizes of the atoms. In this work, the hydrogen absorption and desorption as well as the cycling properties of the TiZrNbHfTa HEA have been studied by in situ Synchrotron X-Ray diffraction, Pressure-Composition-Isotherm, Thermal Desorption Spectroscopy and Differential Scanning Calorimetry. The alloy crystallizes in a cubic bcc phase and undergoes a two-stage hydrogen absorption reaction to a fcc dihydride phase with an intermediate tetragonal monohydride, very similar to the V-H system. The hydrogen absorption/desorption in TiZrNbHfTa is completely reversible and the activation energy of desorption could be calculated. Furthermore, we have observed an interesting macrostructure following parallel planes after the formation of the dihydride phase, which is retained after desorption