Intersex occurrence in rainbow trout (Oncorhynchus mykiss) male fry chronically exposed to ethynylestradiol.

This study aimed to investigate the male-to-female morphological and physiological transdifferentiation process in rainbow trout (Oncorhynchus mykiss) exposed to exogenous estrogens. The first objective was to elucidate whether trout develop intersex gonads under exposure to low levels of estrogen. To this end, the gonads of an all-male population of fry exposed chronically (from 60 to 136 days post fertilization--dpf) to several doses (from environmentally relevant 0.01 µg/L to supra-environmental levels: 0.1, 1 and 10 µg/L) of the potent synthetic estrogen ethynylestradiol (EE2) were examined histologically. The morphological evaluations were underpinned by the analysis of gonad steroid (testosterone, estradiol and 11-ketotestosterone) levels and of brain and gonad gene expression, including estrogen-responsive genes and genes involved in sex differentiation in (gonads: cyp19a1a, ER isoforms, vtg, dmrt1, sox9a2; sdY; cyp11b; brain: cyp19a1b, ER isoforms). Intersex gonads were observed from the first concentration used (0.01 µg EE2/L) and sexual inversion could be detected from 0.1 µg EE2/L. This was accompanied by a linear decrease in 11-KT levels, whereas no effect on E2 and T levels was observed. Q-PCR results from the gonads showed downregulation of testicular markers (dmrt1, sox9a2; sdY; cyp11b) with increasing EE2 exposure concentrations, and upregulation of the female vtg gene. No evidence was found for a direct involvement of aromatase in the sex conversion process. The results from this study provide evidence that gonads of male trout respond to estrogen exposure by intersex formation and, with increasing concentration, by morphological and physiological conversion to phenotypic ovaries. However, supra-environmental estrogen concentrations are needed to induce these changes.

Researchers' roles in knowledge co-production: experience from sustainability research in Kenya, Switzerland, Bolivia and Nepal

Co-production of knowledge between academic and non-academic communities is a prerequisite for research aiming at more sustainable development paths. Sustainability researchers face three challenges in such co-production: (a) addressing power relations; (b) interrelating different perspectives on the issues at stake; and (c) promoting a previously negotiated orientation towards sustainable development. A systematic comparison of four sustainability research projects in Kenya (vulnerability to drought), Switzerland (soil protection), Bolivia and Nepal (conservation vs. development) shows how the researchers intuitively adopted three different roles to face these challenges: the roles of reflective scientist, intermediary, and facilitator of a joint learning process. From this systematized and iterative self-reflection on the roles that a researcher can assume in the indeterminate social space where knowledge is co-produced, we draw conclusions regarding training.

Soil conservation in Swiss agriculture - Approaching abstract and symbolic meanings in farmers' life-worlds

This paper explores the significance of ‘life-worlds’ for better understanding why farmers adopt or reject soil conservation measures and for identifying basic dimensions to be covered by social learning processes in Swiss agricultural soil protection. The study showed that farmers interpret soil erosion and soil conservation measures against the background of their entire life-world. By doing so, farmers consider abstract and symbolic meanings of soil conservation. This is, soil conservation measures have to be feasible and practical in the everyday farming routine, however, they also have to correspond with their aesthetic perception, their value system and their personal and professional identities. Consequently, by switching to soil conservation measures such as no-tillage farmers have to adapt not only the routines of their daily farming life, but also their perception of the aesthetics of cultivated land, underlying values and images of themselves. Major differences between farmers who adopt and farmers who reject no-tillage were found to depend on the degree of coherence they could create between the abstract and symbolic meanings of the soil conservation measure. From this perspective, implementation of soil protection measures faces the challenge of facilitating interactions between farmers, experts and scientists at a ‘deeper’ level, with an awareness of all significant dimensions that characterise the life-world. The paper argues that a certain level of shared symbolic meaning is essential to achieving mutual understanding in social learning processes.

Apnea and oxygen desaturations in children treated with opioids after adenotonsillectomy for obstructive sleep apnea syndrome: a prospective pilot study

Recent case reports have alerted the medical community of fatality in children receiving codeine after tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome.

Prediction of codeine toxicity in infants and their mothers using a novel combination of maternal genetic markers

Substantial variation exists in response to standard doses of codeine ranging from poor analgesia to life-threatening central nervous system (CNS) depression. We aimed to discover the genetic markers predictive of codeine toxicity by evaluating the associations between polymorphisms in cytochrome P450 2D6 (CYP2D6), UDP-glucuronosyltransferase 2B7 (UGT2B7), P-glycoprotein (ABCB1), mu-opioid receptor (OPRM1), and catechol O-methyltransferase (COMT) genes, which are involved in the codeine pathway, and the symptoms of CNS depression in 111 breastfeeding mothers using codeine and their infants. A genetic model combining the maternal risk genotypes in CYP2D6 and ABCB1 was significantly associated with the adverse outcomes in infants (odds ratio (OR) 2.68; 95% confidence interval (CI) 1.61-4.48; P(trend) = 0.0002) and their mothers (OR 2.74; 95% CI 1.55-4.84; P(trend) = 0.0005). A novel combination of the genetic and clinical factors predicted 87% of the infant and maternal CNS depression cases with a sensitivity of 80% and a specificity of 87%. Genetic markers can be used to improve the outcome of codeine therapy and are also probably important for other opioids sharing common biotransformation pathways.

Erlotinib and sorafenib in an orthotopic rat model of hepatocellular carcinoma

The combination of erlotinib with sorafenib is currently being investigated in a phase III RCT. We studied the effect of erlotinib and sorafenib on HCC in a preclinical model.

Suburothelial myofibroblasts in the human overactive bladder and the effect of botulinum neurotoxin type A treatment

BACKGROUND: An increasing body of evidence suggests a possible role of suburothelial myofibroblasts (MFs) in bladder mechanosensation and in the pathophysiology of detrusor overactivity (DO). OBJECTIVE: To determine whether markers of MFs, including gap junction protein connexin43 (Cx43) and c-kit have altered immunohistochemical expression in the suburothelium of patients with neurogenic DO (NDO) or idiopathic DO (IDO) and whether this is affected by successful treatment of DO with botulinum neurotoxin type A (BoNTA). DESIGN, SETTING, AND PARTICIPANTS: Patients with NDO (n=10) or IDO (n=11) were treated in a single-centre, open-label study of intradetrusor BoNTA injections. Control tissue was obtained from 10 patients undergoing pelvic-floor repair procedures who had no overactive bladder (OAB) symptoms. This study is registered with ClinicalTrials.gov, number NCT00662064. INTERVENTIONS: Bladder biopsies performed with flexible cystoscopes were obtained from control subjects and from NDO and IDO patients before BoNTA treatment and at 4 wk and 16 wk after treatment. They were studied with quantitative immunofluorescence using antibodies to connexin 43 (Cx43), vimentin, and c-kit. MEASUREMENTS: Differences in Cx43, vimentin, and c-kit immunoreactivity between control subjects and NDO or IDO patients (primary outcomes). Changes in NDO or IDO, Cx43 immunoreactivity, and c-kit immunoreactivity after BoNTA treatment (secondary outcomes). RESULTS AND LIMITATIONS: Cx43 immunoreactivity was increased in both IDO and NDO patients compared to controls, but remained unchanged after BoNTA treatment. C-kit immunoreactivity was similar in NDO/IDO patients and controls and remained unchanged after BoNTA treatment. CONCLUSIONS: Increased gap junction formation in the suburothelium has been demonstrated in biopsies from humans with DO. It is hypothesised that this change could have a significant role in the pathogenesis of the detrusor abnormality. Successful treatment of NDO or IDO does not appear to be associated with changes in the expression of Cx43 or c-kit on suburothelial MFs.