Pilot Trial of an Emergency Department–based Intervention to Promote Child Passenger Safety Best Practices

BackgroundDespite demonstrated effectiveness of child restraint systems (CRSs), use remains suboptimal. In this randomized pilot trial, we sought to determine the feasibility, acceptability, and potential efficacy of “Tiny Cargo, Big Deal” an ED‐based intervention to promote guideline‐concordant size‐appropriate CRS use.MethodsParents of children < 11 years old were recruited in two EDs and randomized in a 2 × 2 factorial design to four conditions: 1) generic information sheet, 2) tailored brochure mailed after the ED visit, 3) a single motivational interviewing‐based counseling session in the ED, and 4) full intervention (counseling session plus tailored brochure). We assessed feasibility (recruitment, completion, follow‐up rates) and acceptability (parent attitudes, uptake of information) in the ED, at 1 month and at 6 months. We obtained preliminary estimates of effect sizes of the intervention components on appropriate CRS use at 6‐month follow‐up.ResultsOf the 514 parents assessed for eligibility, 456 met inclusion criteria and 347 consented to participate. Enrolled parents were mostly mothers (88.1%); 48.7% were 18 to 29 years old; 52.5% were non‐Hispanic, white; and 65.2% reported size‐appropriate CRS use. Completion rates were 97.7% for baseline survey, 81.6% for counseling, 51.9% for 1‐month follow‐up, and 59.3% for 6‐month follow‐up. In the ED, 70.5% rated thinking about child passenger safety in the ED as very helpful. At 1 month, 70.0% expressed positive attitudes toward the study. Of 132 parents who reported receiving study mailings, 78.9% reviewed the information. Parents randomized to the full intervention demonstrated an increase (+6.12 percentage points) and other groups a decrease (–1.69 to –9.3 percentage points) in the proportion of children reported to use a size‐appropriate CRS at 6‐month follow‐up.ConclusionsSuboptimal CRS use can be identified and intervened upon during a child’s ED visit. A combined approach with ED‐based counseling and mailed tailored brochures shows promise to improve size‐appropriate CRS use.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150596/1/acem13687_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150596/2/acem13687.pd

Yeast Miro GTPase, Gem1p, regulates mitochondrial morphology via a novel pathway

Cell signaling events elicit changes in mitochondrial shape and activity. However, few mitochondrial proteins that interact with signaling pathways have been identified. Candidates include the conserved mitochondrial Rho (Miro) family of proteins, which contain two GTPase domains flanking a pair of calcium-binding EF-hand motifs. We show that Gem1p (yeast Miro; encoded by YAL048C) is a tail-anchored outer mitochondrial membrane protein. Cells lacking Gem1p contain collapsed, globular, or grape-like mitochondria. We demonstrate that Gem1p is not an essential component of characterized pathways that regulate mitochondrial dynamics. Genetic studies indicate both GTPase domains and EF-hand motifs, which are exposed to the cytoplasm, are required for Gem1p function. Although overexpression of a mutant human Miro protein caused increased apoptotic activity in cultured cells (Fransson et al., 2003. J. Biol. Chem. 278:6495–6502), Gem1p is not required for pheromone-induced yeast cell death. Thus, Gem1p defines a novel mitochondrial morphology pathway which may integrate cell signaling events with mitochondrial dynamics

Sexually Transmitted Infection History among Adolescents Presenting to the Emergency Department

BACKGROUND: Adolescents and young adults account for about half of the annual diagnoses of sexually transmitted infections (STI) in the United States. Screening and treatment for STIs, as well as prevention, are needed in health-care settings to help offset the costs of untreated STIs. OBJECTIVE: Our aim was to evaluate the prevalence and correlates of self-reported STI history among adolescents presenting to an emergency department (ED). METHODS: Over two and a half years, 4389 youth (aged 14-20 years) presenting to the ED completed screening measures for a randomized controlled trial. About half (56%) reported lifetime sexual intercourse and were included in analyses examining sexual risk behaviors (e.g., inconsistent condom use), and relationships of STI history with demographics (sex, age, race, school enrollment), reason for ED presentation (i.e., medical or injury), and substance use. RESULTS: Among sexually active youth, 10% reported that a medical professional had ever told them they had an STI (212 females, 35 males). Using logistic regression, female sex, older age, non-Caucasian race, not being enrolled in school, medically related ED chief complaint, and inconsistent condom use were associated with increased odds of self-reported STI history. CONCLUSIONS: One in 10 sexually active youth in the ED reported a prior diagnosed STI. Previous STI was significantly higher among females than males. ED providers inquiring about inconsistent condom use and previous STI among male and female adolescents may be one strategy to focus biological testing resources and improve screening for current STI

Estradiol effects on the dopamine transporter – protein levels, subcellular location, and function

BACKGROUND: The effects of estrogens on dopamine (DA) transport may have important implications for the increased incidence of neurological disorders in women during life stages when hormonal fluctuations are prevalent, e.g. during menarche, reproductive cycling, pregnancy, and peri-menopause. RESULTS: The activity of the DA transporter (DAT) was measured by the specific uptake of (3)H-DA. We found that low concentrations (10(-14 )to 10(-8 )M) of 17β-estradiol (E(2)) inhibit uptake via the DAT in PC12 cells over 30 minutes, with significant inhibition taking place due to E(2 )exposure during only the last five minutes of the uptake period. Such rapid action suggests a non-genomic, membrane-initiated estrogenic response mechanism. DAT and estrogen receptor-α (ERα) were elevated in cell extracts by a 20 ng/ml 2 day NGFβ treatment, while ERβ was not. DAT, ERα and ERβ were also detectable on the plasma membrane of unpermeabilized cells by immunocytochemical staining and by a fixed cell, quantitative antibody (Ab)-based plate assay. In addition, PC12 cells contained RNA coding for the alternative membrane ER GPR30; therefore, all 3 ER subtypes are candidates for mediating the rapid nongenomic actions of E(2). At cell densities above 15,000 cells per well, the E(2)-induced inhibition of transport was reversed. Uptake activity oscillated with time after a 10 nM E(2 )treatment; in a slower room temperature assay, inhibition peaked at 9 min, while uptake activity increased at 3 and 20–30 min. Using an Ab recognizing the second extracellular loop of DAT (accessible only on the outside of unpermeabilized cells), our immunoassay measured membrane vs. intracellular/nonvesicular DAT; both were found to decline over a 5–60 min E(2 )treatment, though immunoblot analyses demonstrated no total cellular loss of protein. CONCLUSION: Our results suggest that physiological levels of E(2 )may act to sequester DAT in intracellular compartments where the transporter's second extramembrane loop is inaccessible (inside vesicles) and that rapid estrogenic actions on this differentiated neuronal cell type may be regulated via membrane ERs of several types

Rat Strain and Housing Conditions Alter Oxidative Stress and Hormone Responses to Chronic Intermittent Hypoxia

Sleep apnea has been associated with elevated risk for metabolic, cognitive, and cardiovascular disorders. Further, the role of hypothalamic–pituitary–adrenal (HPA) activation in sleep apnea has been controversial in human studies. Chronic intermittent hypoxia (CIH) is a rodent model, which mimics the hypoxemia experienced by patients with sleep apnea. Most studies of CIH in rats have been conducted in the Sprague Dawley rat strain. Previously published literature suggests different strains of rats exhibit various responses to disease models, and these effects can be further modulated by the housing conditions experienced by each strain. This variability in response is similar to what has been observed in clinical populations, especially with respect to the HPA system. To investigate if strain or housing (individual or pair-housed) can affect the results of CIH (AHI 8 or 10) treatment, we exposed individual and pair-housed Sprague Dawley and Long-Evans male rats to 7 days of CIH treatment. This was followed by biochemical analysis of circulating hormones, oxidative stress, and neurodegenerative markers. Both strain and housing conditions altered oxidative stress generation, hyperphosphorylated tau protein (tau tangles), circulating corticosterone and adrenocorticotropic hormone (ACTH), and weight metrics. Specifically, pair-housed Long-Evans rats were the most sensitive to CIH, which showed a significant association between oxidative stress generation and HPA activation under conditions of AHI of 8. These results suggest both strain and housing conditions can affect the outcomes of CIH

Alcohol, Tobacco, and Other Drugs: Future Directions for Screening and Intervention in the Emergency Department

This article is a product of a breakout session on injury prevention from the 2009 Academic Emergency Medicine consensus conference on “Public Health in the ED: Screening, Surveillance, and Intervention.” The emergency department (ED) is an important entry portal into the medical care system. Given the epidemiology of substance use among ED patients, the delivery of effective brief interventions (BIs) for alcohol, drug, and tobacco use in the ED has the potential to have a large public health impact. To date, the results of randomized controlled trials of interventional studies in the ED setting for substance use have been mixed in regard to alcohol and understudied in the area of tobacco and other drugs. As a result, there are more questions remaining than answered. The work group developed the following research recommendations that are essential for the field of screening and BI for alcohol, tobacco, and other drugs in the ED. 1) Screening—develop and validate brief and practical screening instruments for ED patients and determine the optimal method for the administration of screening instruments. 2) Key components and delivery methods for intervention—conduct research on the effectiveness of screening, brief intervention, and referral to treatment (SBIRT) in the ED on outcomes (e.g., consumption, associated risk behaviors, and medical psychosocial consequences) including minimum dose needed, key components, optimal delivery method, interventions focused on multiple risk behaviors and tailored based on assessment, and strategies for addressing polysubstance use. 3) Effectiveness among patient subgroups—conduct research to determine which patients are most likely to benefit from a BI for substance use, including research on moderators and mediators of intervention effectiveness, and examine special populations using culturally and developmentally appropriate interventions. 4) Referral strategies—a) promote prospective effectiveness trials to test best strategies to facilitate referrals and access from the ED to preventive services, community resources, and substance abuse and mental health treatment; b) examine impact of available community services; c) examine the role of stigma of referral and follow-up; and d) examine alternatives to specialized treatment referral. 5) Translation—conduct translational and cost-effectiveness research of proven efficacious interventions, with attention to fidelity, to move ED SBIRT from research to practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78664/1/j.1553-2712.2009.00552.x.pd

Effect of Acute Heat Exposure on the Pressor Response to a Voluntary Hypoxic Apnea: A Cross-tolerance Study

The pressor response induced by a voluntary hypoxic apnea is exaggerated in individuals with obstructive sleep apnea and is strongly correlated to sympathetic overactivity. Acute heat exposure alters neural control of blood pressure, but its effect on the pressor response to a voluntary hypoxic apnea has never been explored. PURPOSE: To test the hypothesis that acute heat exposure attenuates the pressor response to a voluntary hypoxic apnea, and thereby manifest as a form of physiological cross-tolerance. METHODS: Eight adults (3 females, 26 ± 2 yrs) were exposed to passive heat stress (water perfused suit) sufficient to increase body core temperature by 1.2 °C. Voluntary hypoxic apneas were performed in duplicate before acute heat exposure (pre-heat) and in recovery when body core temperature returned to ≤ 0.3 °C of baseline. Participants breathed gas mixtures of varying FiO2 (21%, 16%, and 12%; randomized) for 1 min followed immediately by a 15 s end-expiratory apnea. Beat-by-beat arterial blood pressure (Finometer) and arterial oxygen saturation (finger pulse oximetry) were measured throughout. The pressor response was calculated as the difference between baseline mean arterial pressure and the peak response following each apnea. RESULTS: The change in arterial oxygen saturation during each apnea did not differ from pre-heat to recovery (FiO2 21%, pre-heat 0 ± 1 % vs. recovery 0 ± 2 %; FiO2 16%, pre-heat -4 ± 1 % vs. recovery -4 ± 2 %; FiO2 12%, pre-heat -8 ± 3 % vs. recovery -10 ± 4 %; P = 0.3 for interaction). The pressor response to a voluntary apnea was attenuated in recovery from acute heat exposure across all concentrations of FiO2 (FiO2 21%, pre-heat 19 ± 8 mmHg vs. recovery 16 ± 8 mmHg; FiO2 16%, pre-heat 27 ± 8 mmHg vs. recovery 20 ± 8 mmHg; FiO2 12%, pre-heat 33 ± 11 mmHg vs. recovery 27 ± 13 mmHg; P = 0.02 for main effect of time). CONCLUSION: These data suggest that acute heat exposure induces a cross-tolerance effect such that the pressor response to a voluntary hypoxic apnea is reduced. Acute heat exposure could improve hypertension in adults with obstructive sleep apnea, secondary to altered chemoreflex function and sympathetic neural control, and provide additional therapeutic options for this population to improve cardiovascular health

Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins

Autotransporters are a superfamily of virulence factors typified by a channel-forming C terminus that facilitates translocation of the functional N-terminal passenger domain across the outer membrane of Gram-negative bacteria. This final step in the secretion of autotransporters requires a translocation-competent conformation for the passenger domain that differs markedly from the structure of the fully folded secreted protein. The nature of the translocation-competent conformation remains controversial, in particular whether the passenger domain can adopt secondary structural motifs, such as disulfide- bonded segments, while maintaining a secretion-competent state. Here, we used the endogenous and closely spaced cysteine residues of the plasmid-encoded toxin (Pet) from enteroaggregative Escherichia coli to investigate the effect of disulfide bond-induced folding on translocation of an auto-transporter passenger domain. We reveal that rigid structural elements within disulfide-bonded segments are resistant to autotransporter-mediated secretion. We define the size limit of disulfide-bonded segments tolerated by the autotransporter system demonstrating that, when present, cysteine pairs are intrinsically closely spaced to prevent congestion of the translocator pore by large disulfide-bonded regions. These latter data strongly support the hairpin mode of autotransporter biogenesis