Perinatal exposure to the fungicide prochloraz feminizes the male rat offspring.

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.     

The association between symptoms and exposure is stronger in dropouts than in non-dropouts among employees in Norwegian smelters: a five-year follow-up study

Purpose  

We have investigated the association between respiratory symptoms and dust exposure among employees in 18 Norwegian smelters using a longitudinal design.     

Prochloraz: an imidazole fungicide with multiple mechanisms of action

Prochloraz is an imidazole fungicide that is widely used in Europe, Australia, Asia and South America within gardening and agriculture. Screening studies have shown that prochloraz elicits multiple mechanisms of action in vitro, as it antagonizes the androgen and the oestrogen receptor, agonizes the Ah receptor and inhibits aromatase activity. In vivo prochloraz acts as an antiandrogen in the Hershberger assay by reducing weights of reproductive organs, affecting androgen-regulated gene expressions in the prostate and increasing luteinizing hormone levels. In order to investigate the developmental effects of prochloraz, pregnant Wistar dams were dosed perinatally with 30 mg/kg prochloraz. Results showed that prochloraz significantly reduced plasma and testicular testosterone levels in gestational day 21 male foetuses, whereas testicular progesterone was increased. Gestational length was increased by prochloraz. In male pups a significant increase in nipple retention was found, and the weight of the bulbourethral glands was decreased. Behavioural studies showed that the activity level and sweet preference of adult males were significantly increased, indicating that exposure during gestation and lactation causes permanent effects in adulthood. Overall, these results indicate that prochloraz feminizes the male offspring after perinatal exposure, and that these effects are due, at least in part, to diminished fetal steroidogenesis. Thus, a novel endocrine disruptor has been identified that is mechanistically interesting as it elicits dual mechanisms of action and acts as an antiandrogen both by blocking the androgen receptor and by inhibiting fetal steroidogenesis. That a fungicide with such effects is so widely used is a cause for concern, and its use should be reduced, thereby minimizing the risk of human exposure.     

Prediction of dropout from respiratory symptoms and airflow limitation in a longitudinal respiratory study

OBJECTIVES: This study investigated the possibility that employees reporting respiratory symptoms were more likely than asymptomatic workers to dropout of a respiratory study carried out in Norwegian smelters. METHODS: The study included 3924 employees in 24 Norwegian smelters. They were examined annually using a respiratory questionnaire and spirometry. The employees who did not meet for the follow-up within 18 months prior to the end of the study were considered dropouts. The data were analyzed using Cox regression for time-dependent covariates. RESULTS: The total and the median follow-up times were 16 997 and 4.9 years, respectively. The overall dropout rate was 44.5 [95% confidence interval (95% CI) 41.5-47.8 per 1000 person-years]. The hazard ratio (HR) for dropout was 1.38 (95% CI 1.15-1.66) for the workers reporting any respiratory symptom compared with the asymptomatic workers. The effect was the strongest among the employees who reported dyspnea, and it was stronger regarding symptoms at the last visit than for the baseline symptoms. Similarly, the hazard ratio for dropout for those with an airflow limitation [forced expiratory volume/forced vital capacity below the 5th percentile of the predicted value] was 1.31 (95% CI 1.01-1.69) when they were compared with employees without any airflow limitation. CONCLUSIONS: Respiratory symptoms and airflow limitation are important predictors of dropout from a longitudinal respiratory study.     

Impact of the material and sintering protocol,layer thickness,and thermomechanical aging on the two-body wear and fracture load of 4Y-TZP crowns

Clinical Oral Investigations - The aim of this study is to investigate the influence of the material and corresponding sintering protocol, layer thickness, and aging on the two-body wear (2BW) and...     

Interobserver agreement in analysis of cardiotocograms recorded during trial of labor after cesarean

Introduction: To examine interobserver agreement in intrapartum cardiotocography (CTG) classification in women undergoing trial of labor after a cesarean section (TOLAC) at term with or without complete uterine rupture.

Materials and methods: Nineteen blinded and independent Danish obstetricians assessed CTG tracings from 47 women (174 individual pages) with a complete uterine rupture during TOLAC and 37 women (133 individual pages) with no uterine rupture during TOLAC. Individual pages with CTG tracings lasting at least 20?min were evaluated by three different assessors and counted as an individual case. The tracings were analyzed according to the modified version of the Federation of Gynaecology and Obstetrics (FIGO) guidelines elaborated for the use of STAN (ST-analysis). Occurrence of defined abnormalities was recorded and the tracings were classified as normal, suspicious, pathological, or preterminal. The interobserver agreement was evaluated using Fleiss’ kappa.

Results: Agreement on classification of a preterminal CTG was almost perfect. The interobserver agreement on normal, suspicious or pathological CTG was moderate to substantial. Regarding the presence of severe variable decelerations, the agreement was moderate. No statistical difference was found in the interobserver agreement between classification of tracings from women undergoing TOLAC with and without complete uterine rupture.

Conclusions: The interobserver agreement on classification of CTG tracings from high-risk deliveries during TOLAC is best for assessment of a preterminal CTG and the poorest for the identification of severe variable decelerations.     

Risk of death after first-time blood stream infection in incident dialysis patients with specific consideration on vascular access and comorbidity

Background

The mortality following blood stream infection (BSI) and risk of subsequent BSI in relation to dialysis modality, vascular access, and other potential risk factors has received relatively little attention. Consequently, we assessed these matters in a retrospective cohort study, by use of the Danish nation-wide registries.

Methods

Patients more than 17?years of age, who initiated dialysis between 1.1.2010 and 1.1.2014, were grouped according to their dialysis modality and vascular access. Survival was modeled in time-dependent Cox proportional hazard analyses. Potential risk factors confined by a modified Charlson comorbidity index (MCCI), were subsequently assessed in stepwise selection models.

Results

At baseline, 764 patients received peritoneal dialysis (PD), and 434, 479, and 782 hemodialysis (HD) patients were dialyzed by use of arteriovenous fistulas (AVFs), tunneled catheters (TCs), and non-tunneled catheters (NTCs), respectively. We identified 1069 BSIs with an overall incidence rate of 17.7 episodes per 100 person years, and 216 BSIs occurred more than one time in the same patient. HRs of post BSI mortality relative to PD were 3.20 (95% CI 1.86–5.50; p <?0.001) with NTCs; whereas no associations were found for AVF and TC. The risk of subsequent BSIs was higher with NTCs [HR 2.29 (95% CI 1.09–4.82), p =?0.030], and no significant difference was found for AVF and TC, in relation to PD. There was an increased risk of both outcomes with TC relative to AVF [death: 1.57 (95% CI 1.07–2.29, P <?0.021); BSI: 1.78 (95% CI 1.13–2.83, P <?0.014], and risk of death was reduced in patients who changed to AVF after first-time BSI. The MCCI was significantly associated with the risk of subsequent BSI and post BSI death; however, only some of the variables contained in the index were found to be significant risk predictors when analyzed in the fitted model.

Conclusions

While NTC was the most predominant risk factor for subsequent BSI and post BSI mortality, AVF appeared protective.

     

Sexual Picture Processing Interferes with Decision-Making Under Ambiguity

Many people watch sexually arousing material on the Internet in order to receive sexual arousal and gratification. When browsing for sexual stimuli, individuals have to make several decisions, all possibly leading to positive or negative consequences. Decision-making research has shown that decisions under ambiguity are influenced by consequences received following earlier decisions. Sexual arousal might interfere with the decision-making process and should therefore lead to disadvantageous decision-making in the long run. In the current study, 82 heterosexual, male participants watched sexual pictures, rated them with respect to sexual arousal, and were asked to indicate their current level of sexual arousal before and following the sexual picture presentation. Afterwards, subjects performed one of two modified versions of the Iowa Gambling Task in which sexual pictures were displayed on the advantageous and neutral pictures on the disadvantageous card decks or vice versa (n = 41/n = 41). Results demonstrated an increase of sexual arousal following the sexual picture presentation. Decision-making performance was worse when sexual pictures were associated with disadvantageous card decks compared to performance when the sexual pictures were linked to the advantageous decks. Subjective sexual arousal moderated the relationship between task condition and decision-making performance. This study emphasized that sexual arousal interfered with decision-making, which may explain why some individuals experience negative consequences in the context of cybersex use.