Mitochondria as a Target of Environmental Toxicants

Enormous strides have recently been made in our understanding of the biology and pathobiology of mitochondria. Many diseases have been identified as caused by mitochondrial dysfunction, and many pharmaceuticals have been identified as previously unrecognized mitochondrial toxicants. A much smaller but growing literature indicates that mitochondria are also targeted by environmental pollutants. We briefly review the importance of mitochondrial function and maintenance for health based on the genetics of mitochondrial diseases and the toxicities resulting from pharmaceutical exposure. We then discuss how the principles of mitochondrial vulnerability illustrated by those fields might apply to environmental contaminants, with particular attention to factors that may modulate vulnerability including genetic differences, epigenetic interactions, tissue characteristics, and developmental stage. Finally, we review the literature related to environmental mitochondrial toxicants, with a particular focus on those toxicants that target mitochondrial DNA. We conclude that the fields of environmental toxicology and environmental health should focus more strongly on mitochondri

Revisiting the transatlantic divergence over GMOs: Toward a cultural-political analysis

'Revisiting the transatlantic divergence over GMOs: towards a cultural-political analysis' applies a constructivist perspective to the persistent transatlantic divergence over the regulation of GM foods and crops. Political economy and institutionalism have so far dominated the literature. Notwithstanding their crucial insights, this article argues that to achieve a better understanding of the nature and depth of transatlantic regulatory divergence, one should also study prevalent cultural values and identity-related public concerns regarding food and agriculture. These factors can be identified in public opinion trends and have fuelled Europeans' resistance, while contributing to relative regulatory stability in the US. By conceptualizing cultural contexts as catalytic structures, the article also differs from more explicitly discursive accounts of political mobilization. The cultural politics of agricultural biotechnology (agbiotech) relies both on pre-existing values and identities, on the one hand, and on the strategies (and material or other power resources) of political agents

Comparison of Best Versus Worst Clinical Outcomes for Adult Cervical Deformity Surgery.

Study Design: Retrospective cohort study. Objective: Factors that predict outcomes for adult cervical spine deformity (ACSD) have not been well defined. To compare ACSD patients with best versus worst outcomes. Methods: This study was based on a prospective, multicenter observational ACSD cohort. Best versus worst outcomes were compared based on Neck Disability Index (NDI), Neck Pain Numeric Rating Scale (NP-NRS), and modified Japanese Orthopaedic Association (mJOA) scores. Results: Of 111 patients, 80 (72%) had minimum 1-year follow-up. For NDI, compared with best outcome patients (n = 28), worst outcome patients (n = 32) were more likely to have had a major complication ( Conclusions: Factors distinguishing best and worst ACSD surgery outcomes included patient, surgical, and radiographic factors. These findings suggest areas that may warrant greater awareness to optimize patient counseling and outcomes

Tricks and treats: designing technology to support mobility assistance dogs

Assistance dogs are a key intervention to support the autonomy of people with tetraplegia. Previous research on assistive technologies have investigated ways to, ultimately, replace their labour using technology, for instance through the design of smart home environments. However, both the disability studies literature and our interviews suggest there is an immediate need to support these relationships, both in terms of training and bonding. Through a case study of an accessible dog treats dispenser, we investigate a technological intervention responding to these needs, detailing an appropriate design methodology and contributing insights into user requirements and preferences

Physical activity as an aid to smoking cessation during pregnancy: Two feasibility studies

Background: Pharmacotherapies for smoking cessation have not been adequately tested in pregnancy and women are reluctant to use them. Behavioural support alone has a modest effect on cessation rates; therefore, more effective interventions are needed. Even moderate intensity physical activity (e.g. brisk walk) reduces urges to smoke and there is some evidence it increases cessation rates in non-pregnant smokers. Two pilot studies assessed i) the feasibility of recruiting pregnant women to a trial of physical activity for smoking cessation, ii) adherence to physical activity and iii) womens' perceptions of the intervention. Methods: Pregnant smokers volunteered for an intervention combining smoking cessation support, physical activity counselling and supervised exercise (e.g. treadmill walking). The first study provided six weekly treatment sessions. The second study provided 15 sessions over eight weeks. Physical activity levels and continuous smoking abstinence (verified by expired carbon monoxide) were monitored up to eight months gestation. Results: Overall, 11.6% (32/277) of women recorded as smokers at their first antenatal booking visit were recruited. At eight months gestation 25% (8/32) of the women achieved continuous smoking abstinence. Abstinent women attended at least 85% of treatment sessions and 75% (6/8) achieved the target level of 110 minutes/week of physical activity at end-of-treatment. Increased physical activity was maintained at eight months gestation only in the second study. Women reported that the intervention helped weight management, reduced cigarette cravings and increased confidence for quitting. Conclusion: It is feasible to recruit pregnant smokers to a trial of physical activity for smoking cessation and this is likely to be popular. A large randomised controlled trial is needed to examine the efficacy of this intervention

Physical activity for antenatal and postnatal depression in women attempting to quit smoking: randomised controlled trial

Background: Antenatal depression is associated with harmful consequences for both the mother and child. One intervention that might be effective is participation in regular physical activity although data on this question in pregnant smokers is currently lacking. Methods: Women were randomised to six-weekly sessions of smoking cessation behavioural-support, or to the same support plus 14 sessions combining treadmill exercise and physical activity consultations. Results: Among 784 participants (mean gestation 16-weeks), EPDS was significantly higher in the physical activity group versus usual care at end-of-pregnancy (mean group difference (95% confidence intervals (CIs)): 0.95 (0.08 to 1.83). There was no significant difference at six-months postpartum. Conclusion: A pragmatic intervention to increase physical activity in pregnant smokers did not prevent depression at end-of-pregnancy or at six-months postpartum. More effective physical activity interventions are needed in this population. Trial registration: Current Controlled Trials ISRCTN48600346. The trial was prospectively registered on 21/07/2008

Physical activity as an aid to smoking cessation during pregnancy (LEAP) trial: study protocol for a randomized controlled trial

Background: Many women try to stop smoking in pregnancy but fail. One difficulty is that there is insufficient evidence that medications for smoking cessation are effective and safe in pregnancy and thus many women prefer to avoid these. Physical activity (PA) interventions may assist cessation; however, trials examining these interventions have been too small to detect or exclude plausible beneficial effects. The London Exercise And Pregnant smokers (LEAP) trial is investigating whether a PA intervention is effective and cost-effective when used for smoking cessation by pregnant women, and will be the largest study of its kind to date. Methods/design: The LEAP study is a pragmatic, multi-center, two-arm, randomized, controlled trial that will target pregnant women who smoke at least one cigarette a day (and at least five cigarettes a day before pregnancy), and are between 10 and 24 weeks pregnant. Eligible patients are individually randomized to either usual care (that is, behavioral support for smoking cessation) or usual care plus a intervention (entailing supervised exercise on a treadmill plus PA consultations). The primary outcome of the trial is self-reported and biochemically validated continuous abstinence from smoking between a specified quit date and the end of pregnancy. The secondary outcomes, measured at 1 and 4 weeks after the quit date, and at the end of pregnancy and 6 months after childbirth, are PA levels, depression, self-confidence, and cigarette withdrawal symptoms. Smoking status will also be self-reported at 6 months after childbirth. In addition, perinatal measures will be collected, including antenatal complications, duration of labor, mode of delivery, and birth and placental weight. Outcomes will be analyzed on an intention-to-treat basis, and logistic regression models used to compare treatment effects on the primary outcome. Discussion: This trial will assess whether a PA intervention is effective when used for smoking cessation during pregnancy

Precise interpolar phasing of abrupt climate change during the last ice age

The last glacial period exhibited abrupt Dansgaard–Oeschger climatic oscillations, evidence of which is preserved in a variety of Northern Hemisphere palaeoclimate archives¹. Ice cores show that Antarctica cooled during the warm phases of the Greenland Dansgaard–Oeschger cycle and vice versa[superscript 2,3], suggesting an interhemispheric redistribution of heat through a mechanism called the bipolar seesaw[superscript 4–6]. Variations in the Atlantic meridional overturning circulation (AMOC) strength are thought to have been important, but much uncertainty remains regarding the dynamics and trigger of these abrupt events[superscript 7–9]. Key information is contained in the relative phasing of hemispheric climate variations, yet the large, poorly constrained difference between gas age and ice age and the relatively low resolution of methane records from Antarctic ice cores have so far precluded methane-based synchronization at the required sub-centennial precision[superscript 2,3,10]. Here we use a recently drilled high-accumulation Antarctic ice core to show that, on average, abrupt Greenland warming leads the corresponding Antarctic cooling onset by 218 ± 92 years (2σ) for Dansgaard–Oeschger events, including the Bølling event; Greenland cooling leads the corresponding onset of Antarctic warming by 208 ± 96 years. Our results demonstrate a north-to-south directionality of the abrupt climatic signal, which is propagated to the Southern Hemisphere high latitudes by oceanic rather than atmospheric processes. The similar interpolar phasing of warming and cooling transitions suggests that the transfer time of the climatic signal is independent of the AMOC background state. Our findings confirm a central role for ocean circulation in the bipolar seesaw and provide clear criteria for assessing hypotheses and model simulations of Dansgaard–Oeschger dynamics

Routes of Compromise: Road Building and Motor Transportation in Modern Mexico, 1920-1952

Routes of Compromise studies the creation and function of the government bureaucracy that built motor roads and highways, and the everyday impact of those roadways on public life in Mexico. It covers roughly thirty years of construction efforts from 1920 to the early 1950s as foreign and domestic actors, working at the transnational, national, state, and local levels, established a series of policy and investment programs that became the primary model for infrastructure development in Mexico during the mid-twentieth century. Road building offers a unique perspective to the study of Mexican state formation, underscoring how the national government sought to forge public consensus around economic modernization through political compromises that ceded power to state governors and also responded to the particular demands of local communities interested in access to regional motor travel. The field engineers and construction brigades tasked with the technical aspects of this work represented one part of a larger collection of agencies, specialists, politicians, laborers, contractors, and everyday citizens who collaborated on, contested, and ultimately built Mexico\u27s motor road network. This work is a social history of this bureaucracy in Mexico with special attention paid to the evolution of its organizational structure at the state and local levels