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Prochloraz is a commonly used fungicide that has shown multiple mechanisms of action in vitro. It antagonizes the androgen and the estrogen receptors, agonizes the Ah receptor, and inhibits aromatase activity. In vivo prochloraz acts antiandrogenically in the Hershberger assay by reducing weights of reproductive organs, affecting androgen-regulated gene expressions, and increasing luteinizing hormone (LH) levels. The purpose of this study was to investigate reproductive toxic effects after exposure during gestation and lactation to prochloraz alone and a mixture of five pesticides (deltamethrin, methiocarb, prochloraz, simazine, and tribenuron-methyl). Prochloraz (30 mg/kg/day) or the mixture (20 mg/kg/day) was dosed to pregnant Wistar dams from gestational day (GD) 7 until postnatal day (PND) 16. Some dams were taken for cesarean section at GD 21, and others were allowed to give birth. Results showed that prochloraz and the mixture significantly reduced plasma and testicular testosterone levels in GD 21 male fetuses, whereas testicular progesterone was increased. Gestational length was increased by prochloraz. Chemical analysis of the rat breast milk showed that prochloraz was transferred to the milk. In males a significant increase of nipple retention was found, and the bulbourethral gland weight was decreased, whereas other reproductive organs were unaffected. In addition cytochrome P450 (CYP)1A activities in livers were induced by prochloraz, possibly as a result of Ah receptor activation. Behavioral studies showed that the activity level and sweet preference of adult males were significantly increased. Overall these results strongly indicate that prochloraz feminizes the male offspring after perinatal exposure, and that these effects are due, at least in part, to diminished fetal steroidogenesis.  相似文献   
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OBJECTIVE: Community-based lifestyle intervention may offer the best means of reducing the global epidemic of childhood obesity and its consequences, yet few successful interventions have been reported. The objective was to determine whether increasing extra-curricular levels of activity could reduce weight gain in children. METHODS: A controlled intervention study was conducted using standardised methods to assess outcomes. Two comparable relatively rural communities in Otago, New Zealand formed intervention and control settings. Height, weight, waist circumference and participation in physical activity (by accelerometry) were measured at baseline and at 1 year in 384 children aged 5 to 12 years representing the majority of children in this age group in intervention and control communities. Community Activity Co-ordinators were employed at each school in the intervention area. Their brief was to widen exposure to activity and engage children not interested in traditional sporting activities by encouraging lifestyle-based activities (e.g. walking) and non-traditional sports (e.g. golf and taekwondo) during extra-curricular time at school, after school and during vacations. Simple dietary advice was offered and the wider community was encouraged to participate. RESULTS: Average accelerometry counts at 1 year were 28% (95% CI: 11 to 47%) higher in intervention compared with control children after adjusting for age, sex, baseline values and school. Intervention children spent less time in sedentary activity (ratio 0.91, p = 0.007) and more time in moderate (1.07, p = 0.001) and moderate/vigorous (1.10, p = 0.01) activity. Adjusted mean BMI Z-score was lower in intervention relative to control children by -0.12 units (95% CI: -0.22 to -0.02). CONCLUSION:. An intervention designed to maximise opportunities for physical activity during extra-curricular time at school and during leisure time through the provision of community-based Activity Co-ordinators significantly increased participation in physical activity and slowed unhealthy weight gain in primary school-aged children.  相似文献   
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Matching meal insulin to carbohydrate intake, blood glucose, and activity level is recommended in type 1 diabetes management. Calculating an appropriate insulin bolus size several times per day is, however, challenging and resource demanding. Accordingly, there is a need for bolus calculators to support patients in insulin treatment decisions. Currently, bolus calculators are available integrated in insulin pumps, as stand-alone devices and in the form of software applications that can be downloaded to, for example, smartphones. Functionality and complexity of bolus calculators vary greatly, and the few handfuls of published bolus calculator studies are heterogeneous with regard to study design, intervention, duration, and outcome measures. Furthermore, many factors unrelated to the specific device affect outcomes from bolus calculator use and therefore bolus calculator study comparisons should be conducted cautiously. Despite these reservations, there seems to be increasing evidence that bolus calculators may improve glycemic control and treatment satisfaction in patients who use the devices actively and as intended.  相似文献   
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The recognition of psoriasis as a systemic disorder with characteristic skin symptoms and associated diseases has changed treatment concepts substantially. The complexity of psoriasis disease not only requires appropriate therapy but also weight‐loss and smoking cessation programmes as well as trigger factor elimination. The term ‘management’ may better reflect the aim for a holistic approach of disease control. Comorbidity and the presence of psoriatic arthritis are important denominators for drug selection. However, there is a lack of prospective data substantiating a benefit of associated diseases by antipsoriatic therapy. Securing success using treatment goals helps to establish an efficacious therapy and to control inflammation. A regular scoring of disease severity, patients’ quality of life and assessment of other clinically relevant conditions are mandatory to closely follow the disease course. There is debate whether an early treatment may modulate the future course of psoriasis. Concepts of minimal disease activity have not been implemented in psoriasis yet. There is a lack of evidence how long any treatment should be given and when and how to terminate. Finally, outcome tools should specifically be tailored for psoriasis to evaluate disease‐related items as well as the benefit of management from the patient's perspective.  相似文献   
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