Chronic, low-dose rotenone reproduces Lewy neurites found in early stages of Parkinson's disease, reduces mitochondrial movement and slowly kills differentiated SH-SY5Y neural cells

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease, the most common adult neurodegenerative movement disorder, demonstrates a brain-wide pathology that begins pre-clinically with alpha-synuclein aggregates ("Lewy neurites") in processes of gut enteric and vagal motor neurons. Rostral progression into substantia nigra with death of dopamine neurons produces the motor impairment phenotype that yields a clinical diagnosis. The vast majority of Parkinson's disease occurs sporadically, and current models of sporadic Parkinson's disease (sPD) can utilize directly infused or systemic neurotoxins.</p> <p>Results</p> <p>We developed a differentiation protocol for human SH-SY5Y neuroblastoma that yielded non-dividing dopaminergic neural cells with long processes that we then exposed to 50 nM rotenone, a complex I inhibitor used in Parkinson's disease models. After 21 days of rotenone, ~60% of cells died. Their processes retracted and accumulated ASYN-(+) and UB-(+) aggregates that blocked organelle transport. Mitochondrial movement velocities were reduced by 8 days of rotenone and continued to decline over time. No cytoplasmic inclusions resembling Lewy bodies were observed. Gene microarray analyses showed that the majority of genes were under-expressed. qPCR analyses of 11 mtDNA-encoded and 10 nDNA-encoded mitochondrial electron transport chain RNAs' relative expressions revealed small increases in mtDNA-encoded genes and lesser regulation of nDNA-encoded ETC genes.</p> <p>Conclusion</p> <p>Subacute rotenone treatment of differentiated SH-SY5Y neuroblastoma cells causes process retraction and partial death over several weeks, slowed mitochondrial movement in processes and appears to reproduce the Lewy neuritic changes of early Parkinson's disease pathology but does not cause Lewy body inclusions. The overall pattern of transcriptional regulation is gene under-expression with minimal regulation of ETC genes in spite of rotenone's being a complex I toxin. This rotenone-SH-SY5Y model in a differentiated human neural cell mimics changes of early Parkinson's disease and may be useful for screening therapeutics for neuroprotection in that disease stage.</p

Support for e-cigarette regulations among Australian young adults

Background: Surveying support for various regulatory options relating to e-cigarettes can assist policymakers to identify those that have broad support and are therefore likely to be easier to implement. However, data on support for potential e-cigarette regulations in Australia are limited. To inform regulatory efforts, the present study assessed attitudes to the regulation of e-cigarettes among Australian young adults, the most prevalent users of e-cigarettes and therefore the most likely population segment to be affected by e-cigarette regulations. Methods: A total of 1116 Australians aged 18 to 25 years (59% female) completed an online survey where they were presented with various statements relating to the regulation of e-cigarettes and asked to report on the extent to which they agreed or disagreed with each. Statements presented either a restrictive or non-restrictive approach to e-cigarette regulation. Results: Across all statements, 10-22% of respondents responded "don't know" while 23-35% neither agreed nor disagreed, indicating general ambivalence. There was a moderate level of support (33-37%) for regulating e-cigarette sales/use and treating e-cigarettes like tobacco products. Only 20% of respondents were in favour of allowing the use of e-cigarettes in smoke-free areas. Smokers, e-cigarette users, and those who did not believe in the harms associated with e-cigarettes were typically less likely than other respondents to support restrictive approaches. Conclusions: The young Australian adults surveyed were somewhat supportive of restrictions around the sale and use of e-cigarettes, but generally opposed outright bans and any need for a prescription from a medical practitioner. Increasing awareness of the harms associated with the use of e-cigarettes represents a potential strategy to gaining regulatory support

Public, private and personal: Qualitative research on policymakers' opinions on smokefree interventions to protect children in 'private' spaces

<p>Abstract</p> <p>Background</p> <p>Governments use law to constrain aspects of private activities for purposes of protecting health and social wellbeing. Policymakers have a range of perceptions and beliefs about what is public or private. An understanding of the possible drivers of policymaker decisions about where government can or should intervene for health is important, as one way to better guide appropriate policy formation. Our aim was to identify obstacles to, and opportunities for, government smokefree regulation of private and public spaces to protect children. In particular, to seek policymaker opinions on the regulation of smoking in homes, cars and public parks and playgrounds in a country with incomplete smokefree laws (New Zealand).</p> <p>Methods</p> <p>Case study, using structured interviews to ask policymakers (62 politicians and senior officials) about their opinions on new smokefree legislation for public and private places. Supplementary data was obtained from the Factiva media database, on the views of New Zealand local authority councillors about policies for smokefree outdoor public places.</p> <p>Results</p> <p>Overall, interviewees thought that government regulation of smoking in private places was impractical and unwise. However, there were some differences on what <it>was </it>defined as 'private', particularly for cars. Even in public parks, smoking was seen by some as a 'personal' decision, and unlikely to be amenable to regulation. Most participants believed that educative, supportive and community-based measures were better and more practical means of reducing smoking in private places, compared to regulation.</p> <p>Conclusions</p> <p>The constrained view of the role of regulation of smoking in public and private domains may be in keeping with current political discourse in New Zealand and similar Anglo-American countries. Policy and advocacy options to promote additional smokefree measures include providing a better voice for childrens' views, increasing information to policymakers about the harms to children from secondhand smoke and the example of adult smoking, and changing the culture for smoking around children.</p

Costs of vaping: evidence from ITC Four Country Smoking and Vaping Survey

STUDY OBJECTIVES: To compare the prices paid for nicotine vaping products (NVPs) and supplies among current NVP users to prices paid for cigarettes among current smokers. DATA: The 2016 International Tobacco Control Four Country Vaping and Smoking Survey (4CV1). Key measures included: (1) self-reported prices paid for reusable NVPs (eg, rechargeable devices with cartridges and tank system devices with e-liquids) in the 3-month period prior to the survey among current NVP users, (2) prices paid for disposable NVPs, cartridges and e-liquids purchased in the last 30 days among current NVP users and (3) self-reported prices paid for cigarettes among current smokers. RESULTS: Disposable NVP price was higher than the price of a comparable unit for combustible cigarettes in England (EN), USA and Canada (CA). Prefilled cartridge price was higher than the price of a comparable unit of cigarettes in USA and CA, but lower in EN and Australia. E-liquid price was consistently lower than the price of a comparable unit of cigarettes across four countries. For start-up costs, price of a rechargeable device is approximately 3-5 times higher than a pack of cigarettes in four countries. CONCLUSION: NVP prices were generally higher than prices of combustible cigarettes, especially the high upfront NVP devices. The high upfront costs of purchasing a reusable NVP may discourage some smokers from switching to vaping. However, the average lower costs of cartridges and e-liquids relative to a package of cigarettes make switching to a NVP an attractive alternative to smoking in the long term so long as smokers switch completely to vaping

Examining the relationship of vaping to smoking initiation among US youth and young adults: a reality check

BACKGROUND: The 2018 National Academies of Sciences, Engineering, and Medicine Report found substantial evidence that electronic cigarette use (vaping) by youth is strongly associated with an increased risk of ever using cigarettes (smoking) and moderately associated with progressing to more established smoking. However, the Report also noted that recent increases in vaping have been associated with declining rates of youth smoking. This paper examines the temporal relationship between vaping and youth smoking using multiple data sets to explore the question of whether vaping promotes smoking initiation in the USA. METHODS: Using publicly available, nationally representative data on smoking and vaping among youth and young adults, we conducted a trend line analysis of deviations from long-term trends in smoking starting from when vaping became more prevalent. RESULTS: There was a substantial increase in youth vaping prevalence beginning in about 2014. Time trend analyses showed that the decline in past 30-day smoking prevalence accelerated by two to four times after 2014. Indicators of more established smoking rates, including the proportion of daily smokers among past 30-day smokers, also decreased more rapidly as vaping became more prevalent. CONCLUSIONS: The inverse relationship between vaping and smoking was robust across different data sets for both youth and young adults and for current and more established smoking. While trying electronic cigarettes may causally increase smoking among some youth, the aggregate effect at the population level appears to be negligible given the reduction in smoking initiation during the period of vaping's ascendance

Prices, use restrictions and electronic cigarette use-evidence from wave 1 (2016) US data of the ITC Four Country Smoking and Vaping Survey

AIMS: To determine if there are associations between changes in the explicit (i.e. price) and implicit (i.e. use restrictions in public places) costs of cigarettes and nicotine vaping products (NVPs) and their use patterns in the United States. METHODS: Data came from wave 1 (2016) US data of the ITC Four Country Smoking and Vaping Survey (ITC US 4CV1) and Nielsen Scanner Track database. A multiple logistic regression model was applied to estimate the likelihoods of NVP use (vaping at least monthly), cigarette/NVP concurrent use (vaping and smoking at least monthly) and switch from cigarettes to NVPs (had quit smoking  0.05). Higher cigarette prices were associated with greater likelihood of cigarette and NVP concurrent use (P > 0.05). Working in places where vaping is banned is associated with lower likelihood of vaping and NVP and cigarette concurrent use (P > 0.05). CONCLUSIONS: Higher prices for nicotine vaping products (NVPs) and vaping restrictions in public places are associated with less NVP use and less concurrent use of vaping and smoking. Public policies that increase prices for vaping devices and supplies (i.e. regulations, taxes) and restrict where vaping is allowed are likely to suppress vaping

Where Do Vapers Buy Their Vaping Supplies? Findings from the International Tobacco Control (ITC) 4 Country Smoking and Vaping Survey

Aim: This study examines where vapers purchase their vaping refills in countries having different regulations over such devices, Canada (CA), the United States (US), England (EN), and Australia (AU). Methods: Data were available from 1899 current adult daily and weekly vapers who participated in the 2016 (Wave 1) International Tobacco Control Four Country Smoking and Vaping. The outcome was purchase location of vaping supplies (online, vape shop, other). Adjusted odds ratios and 95% confidence intervals were reported for between country comparisons. Results: Overall, 41.4% of current vapers bought their vaping products from vape shops, 27.5% bought them online, and 31.1% from other retail locations. The vast majority of vapers (91.1%) reported using nicotine-containing e-liquids. In AU, vapers were more likely to buy online vs other locations compared to CA (OR = 6.4, 2.3⁻17.9), the US (OR = 4.1, 1.54⁻10.7), and EN (OR = 7.9, 2.9⁻21.8). In the US, they were more likely to buy from vape shops (OR = 3.3, 1.8⁻6.2) or online (OR = 1.9, 1.0⁻3.8) vs other retail locations when compared to those in EN. In CA, vapers were more likely to purchase at vape shops than at other retail locations when compared to vapers in EN (5.9, 3.2⁻10.9) and the US (1.87, 1.0⁻3.1). Conclusions: The regulatory environment and enforcement of such regulations appear to influence the location where vapers buy their vaping products. In AU, banning the retail sale of nicotine vaping products has led vapers to rely mainly on online purchasing sources, whereas the lack of enforcement of the same regulation in CA has allowed specialty vape shops to flourish