Exposure to cigarette taxes as a teenager and the persistence of smoking into adulthood.

Are teenage and adult smoking causally related? Recent anti-tobacco policy is predicated on the assumption that preventing teenagers from smoking will ensure that fewer adults smoke, but direct evidence in support of this assumption is scant. Using data from three nationally representative sources and instrumenting for teenage smoking with cigarette taxes experienced at ages 14-17, we document a strong positive relationship between teenage and adult smoking: deterring 10 teenagers from smoking through raising cigarette taxes roughly translates into 5 fewer adult smokers. We conclude that efforts to reduce teenage smoking can have long-lasting consequences on smoking participation and, presumably, health.

Myths and Methodologies: Standardisation in human physiology research-should we control the controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Myths and Methodologies: Standardisation in Human Physiology Research-Should We Control the Controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

The effects of becoming a physician on prescription drug use and mental health treatment.

There is evidence that physicians disproportionately suffer from substance use disorder and mental health problems. It is not clear, however, whether these phenomena are causal. We use data on Dutch medical school applicants to examine the effects of becoming a physician on prescription drug use and the receipt of treatment from a mental health facility. Leveraging variation from lottery outcomes that determine admission into medical schools, we find that becoming a physician increases the use of antidepressants, anxiolytics, opioids, and sedatives. Increases in the use of antidepressants, anxiolytics, and sedatives are larger among female physicians than among their male counterparts.

Association Between State Antibullying Policies and Suicidal Behaviors Among Lesbian, Gay, Bisexual, and Questioning Youth.

This case-control study uses data from the 2009-2017 Youth Risk Behavior Survey to explore the association between antibullying law adoption and changes in suicidal behaviors among lesbian, gay, bisexual, and questioning youth.

Recreational marijuana laws and the misuse of prescription opioids: Evidence from National Survey on Drug Use and Health microdata.

Several studies have concluded that legalizing medical marijuana can reduce deaths from opioid overdoses. Drawing on micro data from the National Survey on Drug Use and Health, a survey uniquely suited to assessing patterns of substance use, we examine the relationship between recreational marijuana laws (RMLs) and the misuse of prescription opioids. Using a standard difference-in-differences (DD) regression model, we find that RML adoption reduces the likelihood of frequently misusing prescription opioids such as OxyContin, Percocet, and Vicodin. However, using a two-stage procedure designed to account for staggered treatment and dynamic effects, the DD estimate of relationship between RML adoption and the likelihood of frequently misusing prescription opioids becomes positive. Although event study estimates suggest that RML adoption leads to a decrease in the frequency of prescription opioid abuse, this effect appears to dissipate after only 2 or 3 years.

Acyl-Ghrelin Attenuates Neurochemical and Motor Deficits in the 6-OHDA Model of Parkinson's Disease.

The feeding-related hormone, acyl-ghrelin, protects dopamine neurones in murine 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-based models of experimental Parkinson's disease (PD). However, the potential protective effect of acyl-ghrelin on substantia nigra pars compacta (SNpc) dopaminergic neurones and consequent behavioural correlates in the more widely used 6-hydroxydopamine (6-OHDA) rat medial forebrain bundle (MFB) lesion model of PD are unknown. To address this question, acyl-ghrelin levels were raised directly by mini-pump infusion for 7 days prior to unilateral injection of 6-OHDA into the MFB with assessment of amphetamine-induced rotations on days 27 and 35, and immunohistochemical analysis of dopaminergic neurone survival. Whilst acyl-ghrelin treatment was insufficient to elevate food intake or body weight, it attenuated amphetamine-induced circling behaviour and SNpc dopamine neurone loss induced by 6-OHDA. These data support the notion that elevating circulating acyl-ghrelin may be a valuable approach to slow or impair progression of neurone loss in PD.

Automated Quantification of Mitochondrial Fragmentation in an In Vitro Parkinson's Disease Model.

Neuronal mitochondrial fragmentation is a phenotype exhibited in models of neurodegeneration such as Parkinson's disease. Delineating the dysfunction in mitochondrial dynamics found in diseased states can aid our understanding of underlying mechanisms of disease progression and possibly identify novel therapeutic approaches. Advances in microscopy and the availability of intuitive open-access software have accelerated the rate of image acquisition and analysis, respectively. These developments allow routine biology researchers to rapidly turn hypotheses into results. In this protocol, we describe the utilization of cell culture techniques, high-content imaging (HCI), and the subsequent open-source image analysis pipeline for the quantification of mitochondrial fragmentation in the context of a rotenone-based in vitro Parkinson's disease model. © 2020 The Authors. Basic Protocol 1: SN4741 neuron culture and treatment in a rotenone-based model of Parkinson's disease Basic Protocol 2: Identification of cell nuclei, measurement of mitochondrial membrane potential, and measurement of mitochondrial fragmentation in mouse-derived midbrain dopaminergic neurons.

The phenomenon of summer diarrhea and its waning, 1910-1930.

During the first two decades of the 20th century, diarrheal deaths among American infants and children surged every summer. Although we still do not know what pathogen (or pathogens) caused this phenomenon, the consensus view is that it was eventually controlled through public health efforts at the municipal level. Using data from 26 major American cities for the period 1910-1930, we document the phenomenon of summer diarrhea and explore its dissipation. We find that water filtration is associated with a 15 percent reduction in diarrheal mortality among children under the age of two during the non-summer months, but does not seem to have had an effect on diarrheal mortality during the summer. In general, we find little evidence to suggest that public health interventions undertaken at the municipal level contributed to the dissipation of summer diarrhea.

The affordable care act and ambulance response times.

This study contributes to the literature on the capacity challenges faced by health care providers after insurance expansions by examining the Affordable Care Act (ACA) and ambulance response times. Exploiting temporal and geographic variation in the implementation of the ACA as well as pre-treatment differences in uninsured rates, we estimate that the expansions of private and Medicaid coverage under the ACA combined to slow ambulance response times by an average of 24%. We conclude that, through extending coverage to individuals who, in its absence, would not have availed themselves of emergency medical services, the ACA added strain to emergency response systems.

Calorie restriction activates new adult born olfactory-bulb neurones in a ghrelin-dependent manner but acyl-ghrelin does not enhance subventricular zone neurogenesis.

The ageing and degenerating brain show deficits in neural stem/progenitor cell (NSPC) plasticity that are accompanied by impairments in olfactory discrimination. Emerging evidence suggests that the gut hormone ghrelin plays an important role in protecting neurones, promoting synaptic plasticity and increasing hippocampal neurogenesis in the adult brain. In the present study, we investigated the role of ghrelin with respect to modulating adult subventricular zone (SVZ) NSPCs that give rise to new olfactory bulb (OB) neurones. We characterised the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHSR), using an immunohistochemical approach in GHSR-eGFP reporter mice to show that GHSR is expressed in several regions, including the OB but not in the SVZ of the lateral ventricle. These data suggest that acyl-ghrelin does not mediate a direct effect on NSPC in the SVZ. Consistent with these findings, treatment with acyl-ghrelin or genetic silencing of GHSR did not alter NSPC proliferation within the SVZ. Similarly, using a bromodeoxyuridine pulse-chase approach, we show that peripheral treatment of adult rats with acyl-ghrelin did not increase the number of new adult-born neurones in the granule cell layer of the OB. These data demonstrate that acyl-ghrelin does not increase adult OB neurogenesis. Finally, we investigated whether elevating ghrelin indirectly, via calorie restriction (CR), regulated the activity of new adult-born cells in the OB. Overnight CR induced c-Fos expression in new adult-born OB cells but not in developmentally born cells, whereas neuronal activity was absent following re-feeding. These effects were not present in ghrelin-/- mice, suggesting that adult-born cells are uniquely sensitive to changes in ghrelin mediated by fasting and re-feeding. In summary, ghrelin does not promote neurogenesis in the SVZ and OB; however, new adult-born OB cells are activated by CR in a ghrelin-dependent manner.

Association of Ambulance Use in New York City With the Implementation of the Patient Protection and Affordable Care Act.

Importance: Expanding insurance coverage may be associated with overuse of medical care because newly insured patients are insulated from having to pay the full cost. Objective: To examine the use of ambulance transport before and after the rollout of the Patient Protection and Affordable Care Act (ACA) in New York City (NYC), New York. Design, Setting, and Participants: In this case-control study, the volume of ambulance dispatches in NYC for minor injuries before and after the rollout of the ACA was examined. Data were drawn from a census of all ambulance dispatches in NYC between January 1, 2013, and July 31, 2016. Ambulance dispatches for more severe injuries, which are more difficult to characterize as unnecessary, were used as the control group. Analyses were conducted from August 17, 2017, to May, 10, 2019. Main Outcome and Measures: The main outcome was the number of ambulance dispatches for minor injuries, defined per month per dispatch zone. The implementation of the ACA was measured using an indicator variable of 1 for dispatches starting January 1, 2014, and 0 for dispatches before January 1, 2014. The number of ambulance dispatches for injuries and major injuries was used to account for secular trends. Injury severity was classified by the dispatchers based on information from the 911 callers with a severity score on a scale of 1 to 8, where 1 is the most severe; minor injuries had a score of 7; injuries, 5; and major injuries, 3. Results: There were 4 787 180 ambulance dispatches in NYC during the study. After the 2014 expansion of insurance coverage under the ACA, there was an increase in ambulance dispatches for minor injuries compared with dispatches for more severe injuries. Compared with the preimplementation mean (SD) of 20.75 (14.24) minor injury dispatches per dispatch zone per month, there were 7.71 (95% CI, 1.23-14.19) additional minor injury dispatches per dispatch zone per month compared with dispatches for other types of injuries, an increase of 37.2%. Given that NYC has 31 dispatch zones, this increase is equivalent to approximately 239 additional dispatches per month or 2868 additional dispatches per year for minor injuries. Conclusions and Relevance: There was a significant increase in use of ambulance transport for minor injuries in NYC after the ACA insurance expansion, suggesting that the change in health insurance structure was associated with increased use of emergency medical services in nonemergent situations. Future reforms to the US health insurance system should take into account the potential for increased use of emergency medical services in nonemergent situations, which the literature suggests may lead to congestion and slower response times.

Medical marijuana laws and workplace fatalities in the United States.

AIMS: The aim of this research was to determine the association between legalizing medical marijuana and workplace fatalities. DESIGN: Repeated cross-sectional data on workplace fatalities at the state-year level were analyzed using a multivariate Poisson regression. SETTING: To date, 29 states and the District of Columbia have legalized the use of marijuana for medicinal purposes. Although there is increasing concern that legalizing medical marijuana will make workplaces more dangerous, little is known about the relationship between medical marijuana laws (MMLs) and workplace fatalities. PARTICIPANTS: All 50 states and the District of Columbia for the period 1992-2015. MEASUREMENTS: Workplace fatalities by state and year were obtained from the Bureau of Labor Statistics. Regression models were adjusted for state demographics, the unemployment rate, state fixed effects, and year fixed effects. FINDINGS: Legalizing medical marijuana was associated with a 19.5% reduction in the expected number of workplace fatalities among workers aged 25-44 (incident rate ratio [IRR], 0.805; 95% CI, .662-.979). The association between legalizing medical marijuana and workplace fatalities among workers aged 16-24, although negative, was not statistically significant at conventional levels. The association between legalizing medical marijuana and workplace fatalities among workers aged 25-44 grew stronger over time. Five years after coming into effect, MMLs were associated with a 33.7% reduction in the expected number of workplace fatalities (IRR, 0.663; 95% CI, .482-.912). MMLs that listed pain as a qualifying condition or allowed collective cultivation were associated with larger reductions in fatalities among workers aged 25-44 than those that did not. CONCLUSIONS: The results provide evidence that legalizing medical marijuana improved workplace safety for workers aged 25-44. Further investigation is required to determine whether this result is attributable to reductions in the consumption of alcohol and other substances that impair cognitive function, memory, and motor skills.

Ghrelin mediated neuroprotection - A possible therapy for Parkinson's disease?

Parkinson's disease is a common age-related neurodegenerative disorder affecting 10 million people worldwide, but the mechanisms underlying its pathogenesis are still unclear. The disease is characterised by dopamine nerve cell loss in the mid-brain and intra-cellular accumulation of α-synuclein that results in motor and non-motor dysfunction. In this review, we discuss the neuroprotective effects of the stomach hormone, ghrelin, in models of Parkinson's disease. Recent findings suggest that it may modulate mitochondrial function and autophagic clearance of impaired organelle in response to changes in cellular energy balance. We consider the putative cellular mechanisms underlying ghrelin-action and the possible role of ghrelin mimetics in slowing or preventing Parkinson's disease progression. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'

Booster Seat Effectiveness Among Older Children: Evidence From Washington State.

INTRODUCTION: The American Academy of Pediatrics has recommended that children as old as 12 years use a booster seat when riding in motor vehicles, yet little is known about booster seat effectiveness when used by older children. This study estimated the association between booster use and injuries among children aged 8-12 years who were involved in motor vehicle crashes. METHODS: Researchers analyzed data on all motor vehicle crashes involving children aged 8-12 years reported to the Washington State Department of Transportation from 2002 to 2015. Data were collected in 2015 and analyzed in 2016. Children who were in a booster seat were compared with children restrained by a seat belt alone. Logistic regression was used to adjust for potential confounders. RESULTS: In unadjusted models, booster use was associated with a 29% reduction in the odds of experiencing any injury versus riding in a seat belt alone (OR=0.709, 95% CI=0.675, 0.745). In models adjusted for potential confounders, booster use was associated with a 19% reduction in the odds of any injury relative to riding in a seat belt alone (OR=0.814, 95% CI=0.749, 0.884). The risk of experiencing an incapacitating/fatal injury was not associated with booster use. CONCLUSIONS: Children aged 8-12 years involved in a motor vehicle crash are less likely to be injured if in a booster than if restrained by a seat belt alone. Because only 10% of U.S. children aged 8-12 years use booster seats, policies encouraging their use could lead to fewer injuries.

Economic conditions, illicit drug use, and substance use disorders in the United States.

We provide the first analysis of the relationship between economic conditions and the use of illicit drugs other than marijuana. Drawing on US data from 2002 to 2015, we find mixed evidence on the cyclicality of illicit drug use. However, we find robust evidence that economic downturns lead to increases in the intensity of prescription pain reliever use as well as increases in clinically relevant substance use disorders involving opioids. These effects are concentrated among working-age white males with low educational attainment. We conclude that policymakers should consider devoting more, not fewer, resources to treating substance use disorders during economic downturns.

Chromophores in operative surgery: Current practice and rationalized development.

BACKGROUND: Chromophore-containing molecules feature extensively in surgical practice, with synthetic dyes gaining popularity over endogenous optical adjuncts. New applications for chromophores in diagnostics and operative treatment exploit unique chemical structures suited for illuminating target tissues beyond the visual spectrum, ranging from ultraviolet (UV) to near-infrared (NIR). This review outlines the rationale for surgical chromophore application, the weaknesses and risks in each class of these compounds, and areas of foreseeable potential for employment of specialized contrast agents. METHOD: An English-language literature search applied the following Boolean Search String: "dye OR Lake OR Stain OR chromophore" AND "tox$ OR terato* OR carcino$ OR Allerg$ OR surg$ OR clinic" using EMBASE, PUBMED, PUBMED central and OVIDSp, with back-referencing through Web of Knowledge™. RESULTS: Based on the primary literature, this study proposes a surgically relevant classification system of chromophores in current use, which facilitates risk/benefit consideration for the surgeon who employs them, and which facilitates clinically oriented development. CONCLUSIONS: The next stage of development for optically active surgical adjuncts must address practical constraints whilst minimizing risks of adverse effects. Exploiting the technology's full potential also requires improvements in the usefulness of imagery equipment.