Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review.

BACKGROUND: This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction. METHODS: The databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework. RESULTS: Forty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability. DISCUSSION: Most of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis. CONCLUSION: A panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.

Fast 1H-NMR Species Differentiation Method for Camellia Seed Oils Applied to Spanish Ornamentals Plants. Comparison with Traditional Gas Chromatography.

Camellia genus (Theaceae) is comprised of world famous ornamental flowering plants. C. japonica L. and C. sasanqua Thunb are the most cultivated species due to their good adaptation. The commercial interest in this plant linked to its seed oil increased in the last few years due to its health attributes, which significantly depend on different aspects such as species and environmental conditions. Therefore, it is essential to develop fast and reliable methods to distinguish between different varieties and ensure the quality of Camellia seed oils. The present work explores the study of Camellia seed oils by species and location. Two standardized gas chromatography methods were applied and compared with that of data obtained from proton nuclear magnetic resonance spectroscopy (1H-NMR) for fatty acids profiling. The principal component analysis indicated that the proposed 1H-NMR methodology can be quickly and reliably applied to separate specific Camellia species, which could be extended to other species in future works.

Diminishing Cognitive Capacities in an Ever Hotter World: Evidence From an Applicable Power-Law Description.

OBJECTIVE: Modeling and evaluating a series of power law descriptions for boundary conditions of undiminished cognitive capacities under thermal stress. BACKGROUND: Thermal stress degrades cognition, but precisely which components are affected, and to what degree, has yet to be fully determined. With increasing global temperatures, this need is becoming urgent. Power-law distributions have proven their utility in describing differing natural mechanisms, including certain orders of human performance, but never as a rationalization of stress-altered states of attention. METHOD: From a survey of extant empirical data, absolute thresholds for thermal tolerance for varying forms of cognition were identified. These thresholds were then modeled using a rational power-law description. The implications of the veracity of that description were then identified and analyzed. RESULTS: Cognitive performance thresholds under thermal stress are advanced as power-law relationships, t = f(T) = c[(T - Tref)/Tref]-α. Coherent scaling parameters for diverse cognitive functionalities are specified that are consistent with increases in deep (core) body temperature. Therefore, scale invariance provides a "universal constant," viz, 20% detriment in mental performance per 10% increase in T deviation, from a comfortable reference temperature Tref. CONCLUSION: We know the thermal range within which humans can survive is quite narrow. The presented power-law descriptions imply that if making correct decisions is critical for our future existence, then our functional thermal limits could be much more restricted than previously thought. APPLICATION: We provide our present findings, such that others can both assess and mitigate the effects of adverse thermal loads on cognition, in whatever human scenario they occur.

Thermal effects on cognition: a new quantitative synthesis.

There is little doubt that increases in thermal load beyond the thermo-neutral state prove progressively stressful to all living organisms. Increasing temperatures across the globe represent in some locales, and especially for outdoors workers, a significant source of such chronic load increase. However, increases in thermal load affect cognition as well as physical work activities. Such human cognition has perennially been viewed as the primary conduit through which to solve many of the iatrogenic challenges we now face. Yet, thermal stress degrades the power to think. Here, we advance and refine the isothermal description of such cognitive decrements, founded upon a synthesis of extant empirical evidence. We report a series of mathematical functions which describe task-specific patterns of performance deterioration, linking such degrees of decrement to the time/temperature conditions in which they occur. Further, we provide a simple, free software tool to support such calculations so that adverse thermal loads can be monitored, assessed and (where possible) mitigated to preserve healthy cognitive functioning.