Full-Size Off-Highway Vehicle Registration Program, December 30, 2003

Report submitted by the Iowa Department of Natural Resources and the Iowa Department of Transportation to the General Assembly as required by Senate File 458, section 152, passed by the 2003 General Assembly and signed May 30, 2003.

Association of smoking and nicotine dependence with pre-diabetes in young and healthy adults.

INTRODUCTION: Several studies have shown an increased risk of type 2 diabetes among smokers. Therefore, the aim of this analysis was to assess the relationship between smoking, cumulative smoking exposure and nicotine dependence with pre-diabetes. METHODS: We performed a cross-sectional analysis of healthy adults aged 25-41 in the Principality of Liechtenstein. Individuals with known diabetes, Body Mass Index (BMI) >35 kg/m² and prevalent cardiovascular disease were excluded. Smoking behaviour was assessed by self-report. Pre-diabetes was defined as glycosylated haemoglobin between 5.7% and 6.4%. Multivariable logistic regression models were done. RESULTS: Of the 2142 participants (median age 37 years), 499 (23.3%) had pre-diabetes. There were 1,168 (55%) never smokers, 503 (23%) past smokers and 471 (22%) current smokers, with a prevalence of pre-diabetes of 21.2%, 20.9% and 31.2%, respectively (p <0.0001). In multivariable regression models, current smokers had an odds ratio (OR) of pre-diabetes of 1.82 (95% confidential interval (CI) 1.39; 2.38, p <0.0001). Individuals with a smoking exposure of <5, 5-10 and >10 pack-years had an OR (95% CI) for pre-diabetes of 1.34 (0.90; 2.00), 1.80 (1.07; 3.01) and 2.51 (1.80; 3.59) (p linear trend <0.0001) compared with never smokers. A Fagerström score of 2, 3-5 and >5 among current smokers was associated with an OR (95% CI) for pre-diabetes of 1.27 (0.89; 1.82), 2.15 (1.48; 3.13) and 3.35 (1.73; 6.48) (p linear trend <0.0001). DISCUSSION: Smoking is strongly associated with pre-diabetes in young adults with a low burden of smoking exposure. Nicotine dependence could be a potential mechanism of this relationship.

Androgen dependence of hirsutism, acne, and alopecia in women : retrospective analysis or 228 patients investigated for hyperandrogenism

RAPPORT DE SYNTHESE : L'hirsutisme, l'acné et l'alopécie chez la femme sont souvent associés à des troubles menstruels et à une production excessive d'androgènes, raison pour laquelle ces symptômes cutanés font l'objet d'évaluation endocrinienne. L'hyperandrogénie affecte 5 à 10 % des femmes en âge de reproduction et constitue un motif fréquent de consultation. Récemment, les sociétés d'endocrinologie ont émis des recommandations sur l'investigation et le traitement de l'hyperandrogénie. Longtemps confrontés à la demande de patientes souffrant d'hirsutisme, d'acné ou d'alopécie, nous avons décidé d'effectuer une approche diagnostique et thérapeutique comportant des dosages hormonaux et un traitement antiandrogénique. Un grand nombre de patientes a été ainsi étudié au fil des années. Les paramètres mesurés incluaient la testostérone plasmatique totale, l'androstènedione, le sulfate de déhydroépiandrostérone (DHEAS), la sex hormone-binding globulin (SHBG) et la testostérone salivaire. Cette dernière est considérée comme un bon reflet de la testostérone libre plasmatique, indépendamment des protéines de liaison. L'analyse rétrospective des dossiers nous a permis de comparer nos données avec celles de la littérature. Des 318 dossiers de patientes ayant consulté notre Service pour hirsutisme, acné ou alopécie pendant 6 ans, 228 ont pu être retenus pour une évaluation adéquate. Chez les patientes présentant ces symptômes de façon isolée, les taux d'androgènes et la prévalence de l'oligo-aménorhée étaient plus élevés en cas d'hirsutisme qu'en cas d'alopécie, avec des valeurs intermédiaires en cas d'acné. Aucun des androgènes mesurés ne permettait, à lui seul, d'identifier tous les cas d'hyperandrogénie, mais la testostérone salivaire a montré la meilleure corrélation positive avec l'hirsutisme, alors que la testostérone plasmatique totale montrait la moins bonne corrélation, et l'androstènedione, le DHEAS et la SHBG des corrélations intermédiaires (corrélation négative pour la SHBG). De plus, au cours du traitement antiandrogénique, la testostérone salivaire a montré l'abaissement proportionnel le plus marqué de tous les androgénes mesurés. Comparées aux patientes originaires d'Europe centrale, les patientes originaires d'Europe du sud consultaient avec des degrés d'hirsutisme supérieurs, mais aucune différence n'a été observée dans les corrélations entre l'hirsutisme et les taux hormonaux de ces deux groupes. En l'absence d'un nombre suffisant d'échographies ovariennes, .la prévalence du syndrome des ovaires polykystiques a été probablement sous-estimée (63 patientes, 27.6 % des cas), au bénéfice du diagnostic d'hyperandrogénie avec euménorrhée (101, 44.3 %); les autres diagnostics étaient: androgénes normaux (51, 22.4%), SHBG basse isolée (7, 3.1%), hyperplasie surrénalienne congénitale non-classique (4, 1.8%), et tumeur ovarienne (2, 0.9%). Nous avons comparé les divers traitements médicaux de l'hirsutisme publiés au cours des 25 dernières années, quant à leur efficacité et leur coût. La sensibilisation à l'insuline avec metformin est moins efficace, mais aussi moins chère. L'anti-androgène flutamide et l'inhibiteur de la 5-α reductase finastéride figurent parmi les traitements les plus performants, mais ils sont aussi les plus chers. Le traitement anti-androgénique et de suppression hormonale avec acétate de cyprotérone et éthinyloestradiol, utilisé dans cette étude, est également parmi les plus efficaces, tout en étant nettement moins cher. Cette étude est la première comparant directement les taux d'androgènes et la prévalence de l'oligoaménorrhée dans les 3 symptômes cutanés d'hyperandrogénie, hirsutisme, acné et alopécie, et elle démontre leur différente dépendance aux androgènes. La salive apparait comme un milieu de choix pour identifier ces patientes et la recommandation actuelle de doser la testostérone plasmatique totale en premier, pour distinguer l'hyperandrogénie de l'hirsutisme idiopathique, nous paraît inadéquate. Nous proposons, au contraire, d'abandonner ce dosage au profit de celui de la testostérone salivaire. Par ailleurs, notre étude infirme l'hypothèse d'une sensibilité cutanée accrue aux androgènes chez les femmes originaires du sud de l'Europe. Finalement, elle est la seule à comparer les effets cliniques, les changements biologiques et le coût annuel des traitements publiés de l'hirsutisme.

Metabolic equivalent: one size does not fit all.

The metabolic equivalent (MET) is a widely used physiological concept that represents a simple procedure for expressing energy cost of physical activities as multiples of resting metabolic rate (RMR). The value equating 1 MET (3.5 ml O2 x kg(-1) x min(-1) or 1 kcal x kg(-1) x h(-1)) was first derived from the resting O2 consumption (VO2) of one person, a 70-kg, 40-yr-old man. Given the extensive use of MET levels to quantify physical activity level or work output, we investigated the adequacy of this scientific convention. Subjects consisted of 642 women and 127 men, 18-74 yr of age, 35-186 kg in weight, who were weight stable and healthy, albeit obese in some cases. RMR was measured by indirect calorimetry using a ventilated hood system, and the energy cost of walking on a treadmill at 5.6 km/h was measured in a subsample of 49 men and 49 women (26-45 kg/m2; 29-47 yr). Average VO2 and energy cost corresponding with rest (2.6 +/- 0.4 ml O2 x kg(-1) x min(-1) and 0.84 +/- 0.16 kcal x kg(-1) x h(-1), respectively) were significantly lower than the commonly accepted 1-MET values of 3.5 ml O2 x kg(-1) x min(-1) and 1 kcal x kg(-1) x h(-1), respectively. Body composition (fat mass and fat-free mass) accounted for 62% of the variance in resting VO2 compared with age, which accounted for only 14%. For a large heterogeneous sample, the 1-MET value of 3.5 ml O2 x kg(-1) x min(-1) overestimates the actual resting VO2 value on average by 35%, and the 1-MET of 1 kcal/h overestimates resting energy expenditure by 20%. Using measured or predicted RMR (ml O2 x kg(-1) x min(-1) or kcal x kg(-1) x h(-1)) as a correction factor can appropriately adjust for individual differences when estimating the energy cost of moderate intensity walking (5.6 km/h).

Cannabis dependence in Swiss adolescents: An exploration of the role of anxiety, coping styles and psychosocial difficulties

This naturalistic cross-sectional study explores how and to what extent cannabis dependence was associated with intrapersonal aspects (anxiety, coping styles) and interpersonal aspects of adolescent functioning (school status, family relationships, peer relationships, social life). A convenience sample of 110 adolescents (aged 12 to 19) was recruited and subdivided into two groups (38 with a cannabis dependence and 72 nondependent) according to DSM-IV-TR criteria for cannabis dependence. Participants completed the State-Trait Anxiety Inventory (STAI-Y), the Coping Across Situations Questionnaire (CASQ), and the Adolescent Drug Abuse Diagnosis (ADAD) interview investigating psychosocial and interpersonal problems in an adolescent's life. Factors associated with cannabis dependence were explored with logistic regression analyses. The results indicated that severity of problems in social life and peer relationships (OR = 1.68, 95% CI = 1.21 - 2.33) and avoidantcoping (OR = 4.22, 95% CI = 1.01 - 17.73) were the only discriminatory factors for cannabis dependence. This model correctly classified 84.5% of the adolescents. These findings are partially consistent with the "self-medication hypothesis" and underlined the importance of peer relationships and dysfunctional coping strategies in cannabis dependence in adolescence. Limitations of the study and implications for clinical work with adolescents are discussed.

Target Molecular Size and Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis Analysis of the ATP-and Pyrophosphate-Dependent Proton Pumps from Maize Root Tonoplast.

Tonoplast-enriched membranes were prepared from maize (Zea mays L. cv LG 11) primary roots, using sucrose nonlinear gradients. The functional molecular size of the tonoplast ATP-and PPi-dependent proton pumps were analyzed by radiation inactivation. Glucose-6-phosphate dehydrogenase (G6PDH) was added as an internal standard. Frozen samples (-196 degrees C) of the membranes were irradiated with (60)Co for different periods of time. After thawing the samples, the activities of G6PDH, ATPase, and PPase were tested. By applying target theory, the functional sizes of the ATPase and PPase in situ were found to be around 540 and 160 kilodaltons, respectively. The two activities were solubilized and separated by gel filtration chromatography. The different polypeptides copurifying with the two pumps were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two bands (around 59 and 65 kilodaltons) were associated with the ATPase activity, whereas a double band (around 40 kilodaltons) was recovered with the PPase activity.

Pharmacological stimulation of edar signaling in the adult enhances sebaceous gland size and function.

Impaired ectodysplasin A (EDA) receptor (EDAR) signaling affects ectodermally derived structures including teeth, hair follicles, and cutaneous glands. The X-linked hypohidrotic ectodermal dysplasia (XLHED), resulting from EDA deficiency, can be rescued with lifelong benefits in animal models by stimulation of ectodermal appendage development with EDAR agonists. Treatments initiated later in the developmental period restore progressively fewer of the affected structures. It is unknown whether EDAR stimulation in adults with XLHED might have beneficial effects. In adult Eda mutant mice treated for several weeks with agonist anti-EDAR antibodies, we find that sebaceous gland size and function can be restored to wild-type levels. This effect is maintained upon chronic treatment but reverses slowly upon cessation of treatment. Sebaceous glands in all skin regions respond to treatment, although to varying degrees, and this is accompanied in both Eda mutant and wild-type mice by sebum secretion to levels higher than those observed in untreated controls. Edar is expressed at the periphery of the glands, suggesting a direct homeostatic effect of Edar stimulation on the sebaceous gland. Sebaceous gland size and sebum production may serve as biomarkers for EDAR stimulation, and EDAR agonists may improve skin dryness and eczema frequently observed in XLHED.

Cell-free reconstitution of vacuole membrane fragmentation reveals regulation of vacuole size and number by TORC1.

Size and copy number of organelles are influenced by an equilibrium of membrane fusion and fission. We studied this equilibrium on vacuoles-the lysosomes of yeast. Vacuole fusion can readily be reconstituted and quantified in vitro, but it had not been possible to study fission of the organelle in a similar way. Here we present a cell-free system that reconstitutes fragmentation of purified yeast vacuoles (lysosomes) into smaller vesicles. Fragmentation in vitro reproduces physiological aspects. It requires the dynamin-like GTPase Vps1p, V-ATPase pump activity, cytosolic proteins, and ATP and GTP hydrolysis. We used the in vitro system to show that the vacuole-associated TOR complex 1 (TORC1) stimulates vacuole fragmentation but not the opposing reaction of vacuole fusion. Under nutrient restriction, TORC1 is inactivated, and the continuing fusion activity then dominates the fusion/fission equilibrium, decreasing the copy number and increasing the volume of the vacuolar compartment. This result can explain why nutrient restriction not only induces autophagy and a massive buildup of vacuolar/lysosomal hydrolases, but also leads to a concomitant increase in volume of the vacuolar compartment by coalescence of the organelles into a single large compartment.

Individual reproductive success and effective population size in the greater white-toothed shrew Crocidura russula.

In order to investigate the determinants of effective population size in the socially monogamous Crocidura russula, the reproductive output of 44 individuals was estimated through genetic assignment methods. The individual variance in breeding success turned out to be surprisingly high, mostly because the males were markedly less monogamous than expected from previous behavioural data. Males paired simultaneously with up to four females and polygynous males had significantly more offspring than monogamous ones. The variance in female reproductive success also exceeded that of a Poisson distribution (though to a lesser extent), partly because females paired with multiply mated males weaned significantly more offspring. Polyandry also occurred occasionally, but only sequentially (i.e. without multiple paternity of litters). Estimates of the effective to census size ratio were ca. 0.60, which excluded the mating system as a potential explanation for the high genetic variance found in this shrew's populations. Our data suggest that gene flow from the neighbourhood (up to one-third of the total recruitment) is the most likely cause of the high levels of genetic diversity observed in this shrew's subpopulations.

Attenuation of nicotine-induced antinociception, rewarding effects, and dependence in mu-opioid receptor knock-out mice

The involvement of μ-opioid receptors in different behavioral responses elicited by nicotine was explored by using μ-opioid receptor knock-out mice. The acute antinociceptive responses induced by nicotine in the tail-immersion and hot-plate tests were reduced in the mutant mice, whereas no difference between genotypes was observed in the locomotor responses. The rewarding effects induced by nicotine were then investigated using the conditioning place-preference paradigm. Nicotine produced rewarding responses in wild-type mice but failed to produce place preference in knock-out mice, indicating the inability of this drug to induce rewarding effects in the absence of μ-opioid receptors. Finally, the somatic expression of the nicotine withdrawal syndrome, precipitated in dependent mice by the injection of mecamylamine, was evaluated. Nicotine withdrawal was significantly attenuated in knock-out mutants when compared with wild-type mice. In summary, the present results show that μ-opioid receptors are involved in the rewarding responses induced by nicotine and participate in its antinociceptive responses and the expression of nicotine physical dependence.

Size-dependent predation by Dugesia lugubris (Turbellaria) on Physa acuta (Gastropoda): experiments and model

1. We investigated experimentally predation by the flatworm Dugesia lugubris on the snail Physa acuta in relation to predator body length and to prey morphology [shell length (SL) and aperture width (AW)]. 2. SL and AW correlate strongly in the field, but display significant and independent variance among populations. In the laboratory, predation by Dugesia resulted in large and significant selection differentials on both SL and AW. Analysis of partial effects suggests that selection on AW was indirect, and mediated through its strong correlation with SL. 3. The probability P(ij) for a snail of size category i (SL) to be preyed upon by a flatworm of size category j was fitted with a Poisson-probability distribution, the mean of which increased linearly with predator size (i). Despite the low number of parameters, the fit was excellent (r2 = 0.96). We offer brief biological interpretations of this relationship with reference to optimal foraging theory. 4. The largest size class of Dugesia (>2 cm) did not prey on snails larger than 7 mm shell length. This size threshold might offer Physa a refuge against flatworm predation and thereby allow coexistence in the field. 5. Our results are further discussed with respect to previous field and laboratory observations on P acuta life-history patterns, in particular its phenotypic variance in adult body size.

ASTRAL Score Predicts 5-Year Dependence and Mortality in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The ASTRAL score was externally validated showing remarkable consistency on 3-month outcome prognosis in patients with acute ischemic stroke. The present study aimed to evaluate ASTRAL score's prognostic accuracy to predict 5-year outcome. METHODS: All consecutive patients with acute ischemic stroke registered in the Athens Stroke Registry between January 1, 1998, and December 31, 2010, were included. Patients were excluded if admitted >24 hours after symptom onset or if any ASTRAL score component was missing. End points were 5-year unfavorable functional outcome, defined as modified Rankin Scale 3 to 6, and 5-year mortality. For each outcome, the area under the receiver operating characteristics curve was calculated; also, a multivariate Cox proportional hazards analysis was performed to investigate whether the ASTRAL score was an independent predictor of outcome. The Kaplan-Meier product limit method was used to estimate the probability of 5-year survival for each ASTRAL score quartile. RESULTS: The area under the receiver operating characteristics curve of the score to predict 5-year unfavorable functional outcome was 0.89, 95% confidence interval 0.88 to 0.91. In multivariate Cox proportional hazards analysis, the ASTRAL score was independently associated with 5-year unfavorable functional outcome (hazard ratio, 1.09; 95% confidence interval, 1.08-1.10). The area under the receiver operating characteristics curve for the ASTRAL score's discriminatory power to predict 5-year mortality was 0.81 (95% confidence interval, 0.78-0.83). In multivariate analysis, the ASTRAL score was independently associated with 5-year mortality (hazard ratio, 1.09, 95% confidence interval, 1.08-1.10). During the 5-year follow-up, the probability of survival was significantly lower with increasing ASTRAL score quartiles (log-rank test <0.001). CONCLUSIONS: The ASTRAL score reliably predicts 5-year functional outcome and mortality in patients with acute ischemic stroke.

Acceptance of an intended smoking ban in an alcohol dependence clinic.

Alcohol treatment professionals are often reluctant to address tobacco dependence in their patients or to implement smoke-free policies in inpatient treatment programs, fearing, among others, non-adherence to alcohol treatment. The aim of the present study was to evaluate the acceptance of an intended smoking ban in a specialized hospital for alcohol withdrawal. Fifteen of 54 patients reported that they would not begin or quit alcohol treatment if smoking were banned in the clinic, but only five would not begin or quit if nicotine replacement were available. The present study indicates that a non-smoking policy would be feasible in a Swiss alcohol clinic, without jeopardizing alcohol treatment adherence.