Targeting of reactive isolevuglandins in mitochondrial dysfunction and inflammation.

Inflammation is a major cause of morbidity and mortality in Western societies. Despite use of multiple drugs, both chronic and acute inflammation still represent major health burdens. Inflammation produces highly reactive dicarbonyl lipid peroxidation products such as isolevuglandins which covalently modify and cross-link proteins via lysine residues. Mitochondrial dysfunction has been associated with inflammation; however, its molecular mechanisms and pathophysiological role are still obscure. We hypothesized that inflammation-induced isolevuglandins contribute to mitochondrial dysfunction and mortality. To test this hypothesis, we have (a) investigated the mitochondrial dysfunction in response to synthetic 15-E2-isolevuglandin (IsoLG) and its adducts; (b) developed a new mitochondria-targeted scavenger of isolevuglandins by conjugating 2-hydroxybenzylamine to the lipophilic cation triphenylphosphonium, (4-(4-aminomethyl)-3-hydroxyphenoxy)butyl)-triphenylphosphonium (mito2HOBA); (c) tested if mito2HOBA protects from mitochondrial dysfunction and mortality using a lipopolysaccharide model of inflammation. Acute exposure to either IsoLG or IsoLG adducts with lysine, ethanolamine or phosphatidylethanolamine inhibits mitochondrial respiration and attenuates Complex I activity. Complex II function was much more resistant to IsoLG. We confirmed that mito2HOBA markedly accumulates in isolated mitochondria and it is highly reactive with IsoLGs. To test the role of mitochondrial IsoLGs, we studied the therapeutic potential of mito2HOBA in lipopolysaccharide mouse model of sepsis. Mito2HOBA supplementation in drinking water (0.1 g/L) to lipopolysaccharide treated mice increased survival by 3-fold, improved complex I-mediated respiration, and histopathological analyses supported mito2HOBA-mediated protection of renal cortex from cell injury. These data support the role of mitochondrial IsoLG in mitochondrial dysfunction and inflammation. We conclude that reducing mitochondrial IsoLGs may be a promising therapeutic target in inflammation and conditions associated with mitochondrial oxidative stress and dysfunction

The impact of strengthening cigarette pack warnings: Systematic review of longitudinal observational studies

Cigarette pack warnings are a tobacco control strategy used globally. To understand their impact, we systematically reviewed longitudinal observational studies examining national implementation of strengthened warnings

Effects of Strengthening Cigarette Pack Warnings on Attention and Message Processing: A Systematic Review

The current study sought to examine the impact of strengthening cigarette pack warnings on attention, message processing, and perceived effectiveness, through a systematic review of longitudinal observational studies. The review included 22 studies (N = 81,824 participants). Strengthened warnings increased attention to warnings, recall of warnings, and thinking about the health risks of smoking. Strengthened warnings also increased several perceived effectiveness outcomes, including perceptions that warnings reduce smoking and motivate quitting. Strengthened cigarette pack warnings achieve their goal of attracting attention and enhancing motivation to act. Strengthening warning policies should be a priority for tobacco control globally

The impact of strengthening cigarette pack warnings: Systematic review of longitudinal observational studies

Cigarette pack warnings are a tobacco control strategy used globally. To understand their impact, we systematically reviewed longitudinal observational studies examining national implementation of strengthened warnings

Clean, green, and not so mean: Can business save the world?

No matter how you define it, corporate social responsibility (CSR) is a hot topic. From community investing to business ethics to environmental sustainability and beyond, proponents of CSR view the business landscape through a lens that focuses less on profitability and more on the greater good. “Doing well by doing good” is the business world’s new mantra. Concepts of CSR, green business, social entrepreneurship, and peace through commerce have become a focus of research and are inspiring the next generation of businesspeople. The 2010 BRASS Program gave attendees an expert’s view of certain niches within the broader realm of ethical or socially responsible business practices

Climate Change is an Emerging Threat to Perinatal Mental Health

Objective: In this discussion, we build the case for why climate change is an emerging threat to perinatal mental health. Method: A search of current literature on perinatal and maternal mental health and extreme weather events was conducted in PubMed/MEDLINE and Web of Science databases. Only articles focusing on maternal mental health were included in this narrative review. Results: The perinatal period represents a potentially challenging timeframe for women for several reasons. Necessary role adjustments (reprioritization), changes in one’s ability to access pre-birth levels (and types) of social support, fluctuating hormones, changes in body shape, and possible complications during pregnancy, childbirth, or postpartum are just a few of the factors that can impact perinatal mental health. Trauma is also a risk factor for negative mood symptoms and can be experienced as the result of many different types of events, including exposure to extreme weather/natural disasters. Conclusion: While the concepts of “eco-anxiety,” “climate despair,” and “climate anxiety” have garnered attention in the mainstream media, there is little to no discussion of how the climate crisis impacts maternal mental health. This is an important omission as the mother’s mental health impacts the family unit as a whole

Multimessenger Search for Sources of Gravitational Waves and High-Energy Neutrinos: Results for Initial LIGO-Virgo and IceCube

We report the results of a multimessenger search for coincident signals from the LIGO and Virgo gravitational-wave observatories and the partially completed IceCube high-energy neutrino detector, including periods of joint operation between 2007-2010. These include parts of the 2005-2007 run and the 2009-2010 run for LIGO-Virgo, and IceCube's observation periods with 22, 59 and 79 strings. We find no significant coincident events, and use the search results to derive upper limits on the rate of joint sources for a range of source emission parameters. For the optimistic assumption of gravitational-wave emission energy of $10^{-2}$\,M$_\odot$c$^2$ at $\sim 150$\,Hz with $\sim 60$\,ms duration, and high-energy neutrino emission of $10^{51}$\,erg comparable to the isotropic gamma-ray energy of gamma-ray bursts, we limit the source rate below $1.6 \times 10^{-2}$\,Mpc$^{-3}$yr$^{-1}$. We also examine how combining information from gravitational waves and neutrinos will aid discovery in the advanced gravitational-wave detector era

Chronic Kidney Disease and Exposure to Nephrotoxic Metals

Chronic kidney disease (CKD) is a common progressive disease that is typically characterized by the permanent loss of functional nephrons. As injured nephrons become sclerotic and die, the remaining healthy nephrons undergo numerous structural, molecular, and functional changes in an attempt to compensate for the loss of diseased nephrons. These compensatory changes enable the kidney to maintain fluid and solute homeostasis until approximately 75% of nephrons are lost. As CKD continues to progress, glomerular filtration rate decreases, and remaining nephrons are unable to effectively eliminate metabolic wastes and environmental toxicants from the body. This inability may enhance mortality and/or morbidity of an individual. Environmental toxicants of particular concern are arsenic, cadmium, lead, and mercury. Since these metals are present throughout the environment and exposure to one or more of these metals is unavoidable, it is important that the way in which these metals are handled by target organs in normal and disease states is understood completely