Effects of environmental and electric perturbations on the pKa of thioredoxin cysteine 35: a computational study

Here we present a theoretical-computational study dealing with the evaluation of the pKa of the Cysteine residues in Thioredoxin (TRX) and in its complex with the Thioredoxin-interacting protein (TXNIP). The free energy differences between the anionic and neutral form of the Cysteine 32 and 35 have been evaluated by means of the Perturbed Matrix Method with classical perturbations due to both the environment and an exogenous electric field as provided by Molecular Dynamics (MD) simulations. The evaluation of the free energies allowed us to show that the effect of the perturbing terms is to lower the pKa of Cysteine 32 and Cysteine 35 with respect to the free amino-acid. On the other hand, in the complex TRX-TXNIP, our data show an enhanced stabilization of the neutral reduced form of Cys 35. These results suggest that external electric stimuli higher than 0.02 V/nm can modulate the Cysteine pKa, which can be connected to the tight regulation of the TRX acting as an antioxidant agent

Guidelines for limiting exposure to electromagnetic fields (100 kHz to 300 GHz)

Radiofrequency electromagnetic fields (EMFs) are used to enable a number of modern devices, including mobile telecommunications infrastructure and phones, Wi-Fi, and Bluetooth. As radiofrequency EMFs at sufficiently high power levels can adversely affect health, ICNIRP published Guidelines in 1998 for human exposure to time-varying EMFs up to 300 GHz, which included the radiofrequency EMF spectrum. Since that time, there has been a considerable body of science further addressing the relation between radiofrequency EMFs and adverse health outcomes, as well as significant developments in the technologies that use radiofrequency EMFs. Accordingly, ICNIRP has updated the radiofrequency EMF part of the 1998 Guidelines. This document presents these revised Guidelines, which provide protection for humans from exposure to EMFs from 100 kHz to 300 GHz

Gaps in knowledge relevant to the “guidelines for limiting exposure to time-varying electric and magnetic fields (1 Hz-100 kHz)"

Sources of low-frequency fields are widely found in modern society. All wires or devices carrying or using electricity generate extremely low frequency (ELF) electric fields (EFs) and magnetic fields (MFs), but they decline rapidly with distance to the source. High magnetic flux densities are usually found in the vicinity of power lines and close to equipment using strong electrical currents, but can also be found in buildings with unbalanced return currents, or indoor transformer stations. For decades, epidemiological as well as experimental studies have addressed possible health effects of exposure to ELF-MFs. The main goal of ICNIRP is to protect people and the environment from detrimental exposure to all forms of non-ionizing radiation (NIR). To this end, ICNIRP provides advice and guidance by developing and disseminating exposure guidelines based on the available scientific research. Research in the low-frequency range began more than 40 years ago, and there is now a large body of literature available on which ICNIRP set its protection guidelines. A review of the literature has been carried out to identify possible relevant knowledge gaps, and the aim of this statement is to describe data gaps in research that would, if addressed, assist ICNIRP in further developing guidelines and setting revised recommendations on limiting exposure to electric and magnetic fields. It is articulated in two parts: the main document, which reviews the science related to LF data gaps, and the annex, which explains the methodology used to identify the data gaps

Light-emitting diodes (LEDS): Implications for safety

Since the original ICNIRP Statement was published in 2000, there have been significant improvements in the efficiency and radiance (i.e., optical radiation emission) of LEDs. The most important improvement is the development of 'white' LEDs that can be used as general lighting sources, which are more efficient than traditional lighting sources. LEDs emitting in the ultraviolet wavelength region have also become available and have made their way into consumer products. All these changes have led to a rise in concern for the safety of the optical radiation emissions from LEDs. Several in vitro and animal studies have been conducted, which indicate that blue and white LEDs can potentially cause retinal cell damage under high irradiance and lengthy exposure conditions. However, these studies cannot be directly extrapolated to normal exposure conditions for humans, and equivalent effects can also be caused by the optical radiation from other light sources under extreme exposure conditions. Acute damage to the human retina from typical exposure to blue or white LEDs has not been demonstrated. Concern for potential long-term effects, e.g. age-related macular degeneration (AMD), remains based on epidemiological studies indicating a link between high levels of exposure to sunlight and AMD. When evaluating the optical radiation safety of LEDs, it has now been established that published safety standards for lamps, not lasers, should be applied. Thus far, the only clear, acute adverse health effects from LEDs are those due to temporal light modulation (including flicker). Glare can also create visual disturbances when LED light fixtures are not properly designed. Further research is needed on potential health effects from short- and long-term exposure to new and emerging lighting technologies

Principles for non-ionizing radiation protection

In this statement, the International Commission on Non-Ionizing Radiation Protection (ICNIRP) presents its principles for protection against adverse health effects from exposure to non-ionizing radiation. These are based upon the principles for protection against ionizing radiation of the International Commission for Radiological Protection (ICRP) in order to come to a comprehensive and consistent system of protection throughout the entire electromagnetic spectrum. The statement further contains information about ICNIRP and the processes it uses in setting exposure guidelines

Direct use of eazyplex\uae SuperBug CRE assay from positive blood cultures in conjunction with inpatient infectious disease consulting for timely appropriate antimicrobial therapy in Escherichia coli and Klebsiella pneumoniae bloodstream infections

Objectives: To describe a rapid workflow based on the direct detection of Escherichia coli (Ec) and Klebsiella pneumoniae (Kp) producing CTX-M extended-spectrum \u3b2-lactamase (ESBL) and/or carbapenemases (eg, KPC, VIM) from blood cultures (BCs) and the infectious disease (ID) consulting for timely appropriate antimicrobial therapy. Methods: This observational, retrospective study included adult patients with a first episode of Ec or Kp bloodstream infection (BSI) in a large Italian university hospital, where an inpatient ID consultation team (IDCT) has been operational. Results from the BCs tested for detecting bla CTX-M, bla KPC, bla NDM, bla OXA-48-like, and bla VIM genes by the eazyplex\uae SuperBug CRE assay in Ec and Kp organisms had been notified for antimicrobial therapy consulting. Results: In 321 BSI episodes studied, we found that 151 (47.0%) of Ec or Kp organisms harbored bla CTX-M and/or bla KPC and/or bla VIM (meantime from BC collection: 18.5 h). Empirical antimicrobial treatment was appropriate in 21.8% (33/151) of BSIs, namely 5.9% (3/51) of BSIs caused by KPC/VIM producers and 30.0% (30/100) of BSIs caused by CTX-M producers. After notification of results, the IDCT modified antimicrobial therapy (mean time from BC collection: 20 h) such that the proportion of appropriate treatments increased to 84.8% (128/151) of BSIs, namely 70.6% (36/51) of BSIs caused by KPC/VIM producers and 92.0% (92/100) of BSIs caused by CTX-M producers. Conclusion: Our study shows that a rapid diagnostic-driven clinical strategy allowed for early prescription of potentially effective antimicrobial therapy in BSIs caused by CTX-M ESBL- and/or KPC/VIM carbapenemase-producing Ec and Kp organism

Ionic Channel Gating under Electromagnetic Exposure: A Stochastic Model

Researchers interested in the biological effects of electromagnetic (EM) fields are focusing their attention on the behavior of transmembrane ionicchannels and on their kinetic properties. Theoretical studies of the biochemical dynamic properties of the channels have suggested the development of a modelistic approach considering the membrane channel as a non-deterministic state machine. Its behavior is fully described by a set of states, a matrix of transition rates, and a vector for the probability of the machine to be in each single state at a certain instant. In this work astochasticmodel is developed, generating random processes where the probability for each state is an aleatory variable. The model can be applied to both voltage- and ligand-dependent channels, both unexposed and exposed to EM fields. The response of the model, for voltage-dependent channels such as K+, Na+ and Ca2+ in a voltage-clamp situation, is analyzed for sinusoidal EM fields in the ELF range. The results obtained appear more satisfactory than those presented in earlier papers using similar approaches, as this model shows the sensitivity of the channel response to both the frequency and amplitude of the EM stimulation

Effect of microwave radiation on the permeability of carbonic anhydrase loaded unilamellar liposomes

The influence of 2.45 GHz microwave exposure (6 mW/g) on the diffusion processes in enzyme‐loaded unilamellar liposomes as bioreactors was studied. The enzyme carbonic anhydrase (CA) was entrapped into cationic unilamellar vesicles. Previous kinetic experiments showed a very low self‐diffusion rate of the substrate p‐nitrophenyl acetate (PNPA) across intact liposome bilayer. A twofold increase in the diffusion rate of PNPA through the lipid bilayer was observed after 120 min of microwave radiation compared to temperature control samples. The microwave effect was time dependent. The enzyme activity, as a function of increased diffusion of PNPA, rises over 120 min from 22.3% to 80%. The increase in stearylamine concentration reduces the enzyme activity from 80% to 65% at 120 min. No enzyme leakage was observed. © 1994 Wiley‐Liss, Inc. Copyright © 1994 Wiley‐Liss, Inc., A Wiley Compan