Are environmental exposures to selenium, heavy metals, and pesticides risk factors for amyotrophic lateral sclerosis ?

The etiology of sporadic amyotrophic lateral sclerosis (ALS), the most common form of this degenerative disease of the motor neurons, is still unknown, despite extensive investigation of several genetic and environmental potential risk factors. We have reviewed laboratory and epidemiological studies assessing the role of exposure to neurotoxic chemicals (metalloid selenium; heavy metals mercury, cadmium, and lead; pesticides) in ALS etiology by summarizing the results of these investigations and examining their strengths and limitations. Despite limitations in the exposure assessment methodologies typically used in human studies, we found suggestive epidemiological evidence and biologic plausibility for an association between ALS and antecedent overexposure to environmental selenium and pesticides. The relation with mercury, cadmium, and lead appears weaker

Unique cerebrospinal fluid peptides: potential amyotrophic lateral sclerosis biomarkers and etiological factors

Aim: Amyotrophic lateral sclerosis (ALS) is a progressive disease of unknown etiology, characterized by degeneration of motoneurons and skeletal muscle strength decline that progressively evolves to respiratory failure and death. A key point in the therapeutic approach is to understand the pathological processes associated with disease evolution. In spite of intensive research on the molecular/cellular mechanisms involved in ALS initiation and progression disease etiology, unfortunately, poorly understood and there is no efficient specific/decisive treatment for ALS patients. The aims of the present study are to identify specific factors in the cerebrospinal fluid (CSF) of ALS patients and to test their potential relevance to the etiology of this disease. Methods: Peptides were identified by liquid chromatography tandem mass spectrometry (LC-MS/MS). Motor activity of mice was tested by the Rota-rod test and peptide-induced inflammation was assessed by induction nitric oxide synthase activity in BV2 microglia cells. Results: Analysis of CSF samples of ALS patients (n = 15) detected two peptides, C-terminal fragments of transthyretin and osteopontin, which were absent in a control group (n = 15). In addition to being potential biomarker candidates, the relevancy of these peptides to the disease etiology was tested by assessing their effects on motor activity in mice and inflammation model in cell culture. Intranasal administration of the peptides reduced motor activity in the Rota-rod test and activated lipopolysaccharide-induced inflammation in BV2 microglia cells. Conclusions: These findings suggest that during ALS onset and progression two potentially neurotoxic peptides are formed, released, or penetrated the central nervous system thus inducing neuroinflammation and neurodegeneration

Reduced levels of alpha-1-antitrypsin in cerebrospinal fluid of amyotrophic lateral sclerosis patients: a novel approach for a potential treatment

Abstract Background: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative motor neuron disease that involves activation of the immune system and inflammatory response in the nervous system. Reduced level of the immuno-modulatory and anti-inflammatory protein alpha-1-antitrypsin (AAT) is associated with inflammation-related pathologies. The objective of the present is to determine AAT levels and IL-23 in the cerebrospinal fluid (CSF) of ALS patients and control group. Findings: CSF samples from newly diagnosed ALS patients and age-matched controls were analyzed for AAT and IL-23 by ELISA and magnetic luminex screening, respectively. A statistically significant reduction of 45 % in mean AAT levels was observed in the CSF of ALS patients (21.4 μg/ml) as compared to the control group (mean 38.8 μg/ml, p = 0.013). A statistically significant increase of 30.8 % in CSF mean levels of the pro-inflammatory cytokine IL-23 was observed in ALS patients (1647 pg/ml) in comparison to the controls (1259 pg/ml, p = 0.012). A negative correlation coefficient (r = −0.543) was obtained by linear regression analysis of the two measured parameters (p = 0.036). Conclusions: Reduced AAT and elevated IL-23 CSF levels support the notion of neuroinflammatory process occurring in ALS patients. Increasing AAT levels in the patients’ nervous system should be further investigated as a new therapeutic approach and a novel potential tool for ALS treatment

Suppression of environmental health scientists: real-world examples as a basis for action

Pressures on epidemiologists, toxicologists, and on public health scientists to suppress their work are known to occur worldwide. In this article, we share six stories from environmental health scientists about the pressures they faced in their jobs after bringing public health problems to light. The method used to document each of the stories was to invite scientists who attended meetings of the International Society for Environmental Epidemiology to tell their own stories of having experienced research suppression. We then extracted the salient features of each experience into a coherent story, providing references as corroboration where possible. The specific purpose in going public with the six stories presented in this article is to open a conversation to better equip colleagues to stand up to pressures to suppress their work. By publicly sharing the pressures experienced by these scientists in attempts to suppress their scientific work, including intimidation, harassment, threats and/or bullying, other scientists may be better able to withstand such pressures. In the absence of a larger collection of stories, we are unable to identify common approaches taken against suppression. It appears that a focus on scientific excellence and tenacity are two major factors likely to have contributed to the ability to withstand pressure. We encourage others to tell their stories. Bringing examples of these instances to attention will make them familiar enough to be less intimidating should others experience anything similar. Additional documented experiences will expand the base of stories and thus help colleagues to withstand the pressures wielded by special interests. Shining a light on these pressures will remove barriers, not only to advancing the science, but also to protecting the public interest

Marrying Up: The Role of Sex Ratio in Assortative Matching

We assemble a novel dataset to study the impact of male scarcity on marital assortative matching and other marriage market outcomes using the large shock that WWI caused to the number of French men. Using a difference-in-differences approach, we find that post war in regions with higher mortality rates: men were less likely to marry women of lower social classes; men were more likely and women less likely to marry; out-of-wedlock births increased; divorce rates decreased; and the age gap decreased. These findings are consistent with men improving their position in the marriage market as they become scarcer

Marrying up: The role of sex ratio in assortative matching

We assemble a novel dataset to study the impact of male scarcity on marital assortative matching and other marriage market outcomes using the large shock that WWI caused to the number of French men. Using a difference-in-differences approach, we find that postwar in regions with higher mortality rates: men were less likely to marry women of lower social classes; men were more likely and women less likely to marry; out-of-wedlock births increased; divorce rates decreased; and the age gap decreased. These findings are consistent with men improving their position in the marriage market as they become scarcer