Chloral hydrate disrupts mitosis by increasing intracellular free calcium

In examining how chloral hydrate affects mitosis, we found that extracellular application of 0.1% chloral hydrate produced an abrupt rise in cytosolic free Ca2+. Digitized fluorescence microscopy of Fura-2-loaded, mitotic and interphase PtK cells revealed that Ca2+ rose 15 s after chloral hydrate application, peaked within 1 min at a concentration two- to sevenfold above the basal level and then slowly dropped. Bathing cells in 0.1% chloral hydrate caused metaphase spindles to shorten, starting in 1-2 min, and inhibited spindle elongation without affecting chromosome-to-pole movement during anaphase, as determined by phase-contrast observation of living cells. Spindle elongation and chromosome movement were unaffected by intracellular injection of 7.5% chloral hydrate. Extensive mitotic microtubule breakdown occurred after cells were bathed for 7 min in 0.1% chloral hydrate, while interphase microtubules were unaffected as determined by immunofluorescence. The chloral hydrate-induced microtubule breakdown and metaphase spindle shortening were prevented by 10 mM-CoCl2, which has previously been shown to block Ca2+ influx and to stabilize microtubules in vitro. These results imply that disruption of mitotic spindle function and structure by chloral hydrate is due to a rise in cytosolic free Ca2+, and also indicate that mitotic microtubules are more Ca2+-labile than interphase microtubules

Resistance to Peer influence Moderates the Relationship Between Perceived (But Not Actual) Peer Norms and Binge Drinking in a College Student Social Network

Introduction: Adolescent and young adult binge drinking is strongly associated with perceived social norms and the drinking behavior that occurs within peer networks. The extent to which an individual is influenced by the behavior of others may depend upon that individual’s resistance to peer influence (RPI). Methods: Students in their first semester of college (N = 1323; 54.7% female, 57% White, 15.1% Hispanic) reported on their own binge drinking, and the perceived binge drinking of up to 10 important peers in the first-year class. Using network autocorrelation models, we investigated cross-sectional relationships between participant’s binge drinking frequency and the perceived and actual binge drinking frequency of important peers. We then tested the moderating role of RPI, expecting that greater RPI would weaken the relationship between perceived and actual peer binge drinking on participant binge drinking. Results: Perceived and actual peer binge drinking were statistically significant predictors of participant binge drinking frequency in the past month, after controlling for covariates. RPI significantly moderated the association between perceptions of peer binge drinking and participant’s own binge drinking; this association was weaker among participants with higher RPI compared to those with lower RPI. RPI did not interact with the actual binge drinking behavior of network peers

Longitudinal Research on Aging Drivers (LongROAD): study design and methods

Background: As an important indicator of mobility, driving confers a host of social and health benefits to older adults. Despite the importance of safe mobility as the population ages, longitudinal data are lacking about the natural history and determinants of driving safety in older adults. Methods: The Longitudinal Research on Aging Drivers (LongROAD) project is a multisite prospective cohort study designed to generate empirical data for understanding the role of medical, behavioral, environmental and technological factors in driving safety during the process of aging. Results: A total of 2990 active drivers aged 65–79 years at baseline have been recruited through primary care clinics or health care systems in five study sites located in California, Colorado, Maryland, Michigan, and New York. Consented participants were assessed at baseline with standardized research protocols and instruments, including vehicle inspection, functional performance tests, and “brown-bag review” of medications. The primary vehicle of each participant was instrumented with a small data collection device that records detailed driving data whenever the vehicle is operating and detects when a participant is driving. Annual follow-up is being conducted for up to three years with a telephone questionnaire at 12 and 36 months and in-person assessment at 24 months. Medical records are reviewed annually to collect information on clinical diagnoses and healthcare utilization. Driving records, including crashes and violations, are collected annually from state motor vehicle departments. Pilot testing was conducted on 56 volunteers during March–May 2015. Recruitment and enrollment were completed between July 2015 and March 2017. Conclusions: Results of the LongROAD project will generate much-needed evidence for formulating public policy and developing intervention programs to maintain safe mobility while ensuring well-being for older adults

Associations between parental broader autism phenotype and child autism spectrum disorder phenotype in the Study to Explore Early Development

The autism spectrum disorder phenotype varies by social and communication ability and co-occurring developmental, behavioral, and medical conditions. Etiology is also diverse, with myriad potential genetic origins and environmental risk factors. Examining the influence of parental broader autism phenotype—a set of sub-clinical characteristics of autism spectrum disorder—on child autism spectrum disorder phenotypes may help reduce heterogeneity in potential genetic predisposition for autism spectrum disorder. We assessed the associations between parental broader autism phenotype and child phenotype among children of age 30–68 months enrolled in the Study to Explore Early Development (N = 707). Child autism spectrum disorder phenotype was defined by a replication of latent classes derived from multiple developmental and behavioral measures: Mild Language Delay with Cognitive Rigidity, Mild Language and Motor Delay with Dysregulation (e.g. anxiety/depression), General Developmental Delay, and Significant Developmental Delay with Repetitive Motor Behaviors. Scores on the Social Responsiveness Scale-Adult measured parent broader autism phenotype. Broader autism phenotype in at least one parent was associated with a child having increased odds of being classified as mild language and motor delay with dysregulation compared to significant developmental delay with repetitive motor behaviors (odds ratio: 2.44; 95% confidence interval: 1.16, 5.09). Children of parents with broader autism phenotype were more likely to have a phenotype qualitatively similar to broader autism phenotype presentation; this may have implications for etiologic research

Knowledge of Oral Cancer and Screening Practices of Primary Care Providers at Federally Qualified Health Centers

Objectives: Primary care providers (PCPs) who worked in Federally-Qualified Health Centers (FQHC) in Michigan were surveyed to assess their knowledge level and practices related to screening and preventing oral cancer. Methods: A questionnaire was developed with the assistance of dental and medical experts, and revised through focus groups. The questionnaire included one case scenario describing a suspicious oral lesion in a 55-year old female patient, followed by questions assessing PCPs' knowledge level, attitude, opinion, and screening practices for oral cancer. This mail survey was conducted in 2003. Results: Survey response rate was 56.4%. Over 70% of the respondents reported that they screen patients for oral cancer during a routine physical examination. Forty-four percent of PCPs had high knowledge level, based on the scenario questions. Those who had high knowledge level were more likely to be physicians, males, and more likely to perform screening for oral cancer than those with low knowledge level. There was no difference in age and race/ethnicity between high and low knowledge groups. Perceived barriers included (1) lack of education; (2) lack of specialists to refer patients; and (3) lack of reimbursement. Conclusions: The majority of PCPs in this survey had positive attitudes about performing screening for oral cancer. To involve PCPs in screening for oral cancer, oral health programs should focus on providing up-to-date education, setting up a referral system, and providing proper reimbursement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65814/1/j.1752-7325.2005.tb02806.x.pd

A Phenotype of Childhood Autism Is Associated with Preexisting Maternal Anxiety and Depression

This study explored whether ASD phenotypes in the child were associated with a history of anxiety or depression in the mother. We hypothesized that an ASD profile in children characterized by mild delays and increased rates of dysregulation would be associated with preexisting maternal anxiety or depression. Participants were 672 preschool children with ASD and their mothers. Children were classified as ASD after a comprehensive developmental evaluation. Mothers reported whether a healthcare provider ever diagnosed them with anxiety or depression before the birth of their child. Four child ASD phenotypes were derived from latent class analysis: Mild Language Delay with Cognitive Rigidity (Type 1), Significant Developmental Delay with Repetitive Motor Behaviors (Type 2), General Developmental Delay (Type 3), and Mild Language and Motor Delay with Dysregulation (i.e., aggression, anxiety, depression, emotional reactivity, inattention, somatic complaints, and sleep problems) (Type 4). Type 2 ASD served as the referent category in statistical analyses. Results showed that 22.6% of mothers reported a diagnosis of anxiety or depression before the birth of their child. Maternal anxiety or depression was associated with 2.7 times the odds (95% confidence interval: 1.4, 5.3) of Type 4 or Dysregulated ASD in the child; maternal anxiety and depression was associated with 4.4 times the odds (95% confidence interval: 1.4, 14.0) of Type 4 or Dysregulated ASD in the child. Our findings suggest an association between Dysregulated ASD in the child and anxiety and depression in the mother. These findings can enhance screening methods and inform future research efforts

Demographic and Operational Factors Predicting Study Completion in a Multisite Case-Control Study of Preschool Children

Participant attrition can limit inferences drawn from study results and inflate research costs. We examined factors associated with completion of the Study to Explore Early Development (2007-2011), a multiple-component, case-control study of risk factors for autism spectrum disorder in preschoolers, conducted in California, Colorado, Georgia, Maryland, North Carolina, and Pennsylvania. Participants (n = 3,769) were asked to complete phone interviews, questionnaires, an in-person evaluation, and biologic sampling. We examined whether participant demographic and administrative factors predicted completion using mixed-effects logistic regression models. Completion of individual key study components was generally 70% or higher. However, 58% of families completed all per-protocol data elements (defined a priori as key study components). Per-protocol completion differed according to mother's age, race, educational level, driving distance to clinic, number of contact attempts to enroll, and number of telephone numbers provided (all P < 0.05). Case status was not associated with completion, despite additional data collection for case-confirmation. Analysis of a subset that completed an early interview revealed no differences in completion by household factors of income, primary language spoken, number of adults, or number of children with chronic conditions. Differences in completion by race and education were notable and need to be carefully considered in developing future recruitment and completion strategies

Peri-Pregnancy Cannabis Use and Autism Spectrum Disorder in the Offspring: Findings from the Study to Explore Early Development

The association of autism spectrum disorder (ASD) with self-reported maternal cannabis use from 3 months pre-conception to delivery (“peri-pregnancy”) was assessed in children aged 30–68 months, born 2003 to 2011. Children with ASD (N = 1428) were compared to children with other developmental delays/disorders (DD, N = 1198) and population controls (POP, N = 1628). Peri-pregnancy cannabis use was reported for 5.2% of ASD, 3.2% of DD and 4.4% of POP children. Adjusted odds of peri-pregnancy cannabis use did not differ significantly between ASD cases and DD or POP controls. Results were similar for any use during pregnancy. However, given potential risks suggested by underlying neurobiology and animal models, further studies in more recent cohorts, in which cannabis use and perception may have changed, are needed

Early life influences on child weight outcomes in the Study to Explore Early Development

We examined associations between child body mass index at 2–5 years and maternal pre-pregnancy body mass index, gestational weight gain, and rapid weight gain during infancy in children with autism spectrum disorder, developmental delays, or population controls. The Study to Explore Early Development is a multi-site case–control study of children, aged 2–5 years, classified as autism spectrum disorder (n = 668), developmental delays (n = 914), or population controls (n = 884). Maternal gestational weight gain was compared to the Institute of Medicine recommendations. Rapid weight gain was a change in weight-for-age z-scores from birth to 6 months > 0.67 standard deviations. After adjusting for case status, mothers with pre-pregnancy overweight/obesity were 2.38 times (95% confidence interval: 1.96–2.90) more likely, and mothers who exceeded gestational weight gain recommendations were 1.48 times (95% confidence interval: 1.17–1.87) more likely, to have an overweight/obese child than other mothers (P < 0.001). Children with autism spectrum disorder showed the highest frequency of rapid weight gain (44%) and were 3.47 times (95% confidence interval: 1.85–6.51) more likely to be overweight/obese as children with autism spectrum disorder without rapid weight gain (P < 0.001). Helping mothers achieve a healthy pre-pregnancy body mass index and gestational weight gain represent important targets for all children. Healthy infant growth patterns carry special importance for children at increased risk for an autism spectrum disorder diagnosis

Cost-effectiveness of interventions for increasing the possession of functioning smoke alarms in households with pre-school children: a modelling study

Background The UK has one of the highest rates for deaths from fire and flames in children aged 0-14 years compared to other high income countries. Evidence shows that smoke alarms can reduce the risk of fire-related injury but little exists on their cost-effectiveness. We aimed to compare the cost effectiveness of different interventions for the uptake of 'functioning' smoke alarms and consequently for the prevention of fire-related injuries in children in the UK. Methods We carried out a decision model-based probabilistic cost-effectiveness analysis. We used a hypothetical population of newborns and evaluated the impact of living in a household with or without a functioning smoke alarm during the first 5 years of their life on overall lifetime costs and quality of life from a public health perspective. We compared seven interventions, ranging from usual care to more complex interventions comprising of education, free/low cost equipment giveaway, equipment fitting and/or home safety inspection. Results Education and free/low cost equipment was the most cost-effective intervention with an estimated incremental cost-effectiveness ratio of [pound sign]34,200 per QALY gained compared to usual care. This was reduced to approximately £4,500 per QALY gained when 1.8 children under the age of 5 were assumed per household. Conclusions Assessing cost-effectiveness, as well as effectiveness, is important in a public sector system operating under a fixed budget restraint. As highlighted in this study, the more effective interventions (in this case the more complex interventions) may not necessarily be the ones considered the most cost-effective