Mode of action, concentrations and effects of tributyltin in common shrimp <i>Crangon crangon</i>

With an annual catch of 35,000 – 50,000 tons and a commercial value of roughly €100 million, common shrimp is one of the most valuable European fisheries and aquaculture commodities. Since the late 1960s, European landings strongly decreased until 1990, due to a strongly reduced shrimp abundance and reproduction. In the Wadden Sea, the shrimp stock and hence landed volumes recovered slowly after 1990 to record landings in 2010. In the Southern Bight (i.e. Northern France to Dutch Delta), one of the busiest international shipping lanes, the stock only recovered after 2003. Until now, no explanation was found for these abnormal long-term trends in the shrimp stock. The use of TBT as antifouling agent began in the 1960s, leading to exuberant TBT concentrations in the 1970s and 1980s, especially nearby recreational marinas, shipping lanes, and industrial harbours. At the end of the 1980s, the use of TBT on smaller ship ( 25 m) was only accepted in 2003 and finally entered-into-force in 2008. In 2004, Nishikawa et al. (2004) proved that TBT mimics vertebrate hormone signalling by activating the retinoid-X-receptor (RXR). As this receptor is strongly conserved in the animal kingdom, an identical mode of action (MOA) was generally accepted to have caused the observed reproductive and developmental defects in marine shellfish and gastropods. RXR is a nuclear receptor (NR) believed to directly modulate (i.e. by heterodimerization) the activity of many other NRs. NRs are the major targets of lipophilic hormones (e.g. steroids), and directly induce tissue specific expression of genes involved in development, reproduction, immune response, etc. Within this PhD-thesis, three main research questions were addressed. (1) Does TBT affect the functionality of the shrimp RXR receptor?, (2) what is the temporal and spatial distribution of TBT in North Sea shrimp, and finally (3) do the TBT concentrations observed in the North Sea disrupt shrimp endocrine functioning

Laboratory study of the impact of repetitive electrical and mechanical stimulation on brown shrimp Crangon crangon

Pulse trawling is currently the best available alternative to beam trawling in the brown shrimp Crangon crangon and Sole Solea solea (also known as Solea vulgaris) fisheries. To evaluate the effect of repetitive exposure to electrical fields, brown shrimp were exposed to the commercial electrodes and pulse settings used to catch brown shrimp (shrimp startle pulse) or Sole (Sole cramp pulse) 20 times in 4 d and monitored for up to 14 d after the first exposure. Survival, egg loss, molting, and the degree of intranuclear bacilliform virus (IBV) infection were evaluated and compared with those in stressed but not electrically exposed (procedural control) and nonstressed, nonexposed (control) brown shrimp as well as brown shrimp exposed to mechanical stimuli. The lowest survival at 14 d (57.3%) occurred in the Sole cramp pulse treatment, and this was significantly lower than in the group with the highest survival, the procedural control (70.3%). No effect of electrical stimulation on the severity of IBV infection was found. The lowest percentage of molts occurred in the repetitive mechanical stimulation treatment (14.0%), and this was significantly lower than in the group with the highest percentage of molts, the procedural control (21.7%). Additionally, the mechanically stimulated brown shrimp that died during the experiment had a significantly larger size than the surviving individuals. Finally, no effect of the shrimp startle pulse was found. Therefore, it can be concluded that repetitive exposure to a cramp stimulus and mechanical stimulation may have negative effects on the growth and/or survival of brown shrimp. However, there is no evidence that electrical stimulation during electrotrawls would have a larger negative impact on brown shrimp stocks than mechanical stimulation during conventional beam trawling

Accuracy of single progesterone test to predict early pregnancy outcome in women with pain or bleeding: Meta-analysis of cohort studies

Objective To determine the accuracy with which a single progesterone measurement in early pregnancy discriminates between viable and non-viable pregnancy. Design Systematic review and meta-analysis of diagnostic accuracy studies. Data sources Medline, Embase, CINAHL, Web of Science, ProQuest, Conference Proceedings Citation Index, and the Cochrane Library from inception until April 2012, plus reference lists of relevant studies. Study selection Studies were selected on the basis of participants (women with spontaneous pregnancy of less than 14 weeks of gestation); test (single serum progesterone measurement); outcome (viable intrauterine pregnancy, miscarriage, or ectopic pregnancy) diagnosed on the basis of combinations of pregnancy test, ultrasound scan, laparoscopy, and histological examination; design (cohort studies of test accuracy); and sufficient data being reported. Results 26 cohort studies, including 9436 pregnant women, were included, consisting of 7 studies in women with symptoms and inconclusive ultrasound assessment and 19 studies in women with symptoms alone. Among women with symptoms and inconclusive ultrasound assessments, the progesterone test (5 studies with 1998 participants and cut-off values from 3.2 to 6 ng/mL) predicted a non-viable pregnancy with pooled sensitivity of 74.6% (95% confidence interval 50.6% to 89.4%), specificity of 98.4% (90.9% to 99.7%), positive likelihood ratio of 45 (7.1 to 289), and negative likelihood ratio of 0.26 (0.12 to 0.57). The median prevalence of a non-viable pregnancy was 73.2%, and the probability of a non-viable pregnancy was raised to 99.2% if the progesterone was low. For women with symptoms alone, the progesterone test had a higher specificity when a threshold of 10 ng/mL was used (9 studies with 4689 participants) and predicted a non-viable pregnancy with pooled sensitivity of 66.5% (53.6% to 77.4%), specificity of 96.3% (91.1% to 98.5%), positive likelihood ratio of 18 (7.2 to 45), and negative likelihood ratio of 0.35 (0.24 to 0.50). The probability of a non-viable pregnancy was raised from 62.9% to 96.8%. Conclusion A single progesterone measurement for women in early pregnancy presenting with bleeding or pain and inconclusive ultrasound assessments can rule out a viable pregnancy.Jorine Verhaegen, Ioannis D Gallos, Norah M van Mello, Mohamed Abdel-Aziz, Yemisi Takwoingi, Hoda Harb, Jonathan J Deeks, Ben W J Mol, Arri Coomarasam

Lipid-lowering therapy and risk-based LDL-C goal attainment in Belgium: DA VINCI observational study

Background Cardiovascular disease (CVD) is one of the leading causes of death in Belgium. Current strategies for the prevention and management of CVD focus on reducing low-density lipoprotein cholesterol (LDL-C) levels. This analysis assessed whether LDL-C goals, recommended by the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines, were being achieved in a Belgian study population. Methods The cross-sectional, observational, DA VINCI study enrolled patients prescribed lipid-lowering therapy (LLT) between 21 June 2017 and 20 November 2018. Data for patients from Belgium were extracted for this country-specific analysis. Primary endpoint was the proportion of patients who achieved 2016 ESC/EAS risk-based LDL-C goals; attainment of 2019 risk-based LDL-C goals was evaluated post hoc. Results Of 497 enrolled patients, 41% were female and mean age was 68 years. Among subjects with an LDL-C measurement on stabilised LLT, moderate-intensity statin monotherapy was the most prescribed LLT regimen (59%). Overall, 63% of patients achieved their risk-based LDL-C goals according to the 2016 ESC/EAS guidelines. Among patients with established ASCVD, risk-based LDL-C goal attainment was higher in patients with peripheral arterial disease (53%) than patients with coronary (37%) and cerebrovascular disease (42%). According to the updated 2019 ESC/EAS guidelines, less than half (41%) of patients achieved their risk-based LDL-C goal. The proportion of primary and secondary prevention patients who achieved 2019 risk-based LDL-C goals was 59% and 18%, respectively. Conclusion These findings reveal a large gap between the LDL-C goals advocated by the ESC/EAS and the levels achieved in routine clinical practice in Belgium

Comprehensive genetic dissection of wood properties in a widely-grown tropical tree: Eucalyptus

Background: Eucalyptus is an important genus in industrial plantations throughout the world and is grown for use as timber, pulp, paper and charcoal. Several breeding programmes have been launched worldwide to concomitantly improve growth performance and wood properties (WPs). In this study, an interspecific cross between Eucalyptus urophylla and E. grandis was used to identify major genomic regions (Quantitative Trait Loci, QTL) controlling the variability of WPs. Results: Linkage maps were generated for both parent species. A total of 117 QTLs were detected for a series of wood and end-use related traits, including chemical, technological, physical, mechanical and anatomical properties. The QTLs were mainly clustered into five linkage groups. In terms of distribution of QTL effects, our result agrees with the typical L-shape reported in most QTL studies, i.e. most WP QTLs had limited effects and only a few (13) had major effects (phenotypic variance explained &gt; 15%). The co-locations of QTLs for different WPs as well as QTLs and candidate genes are discussed in terms of phenotypic correlations between traits, and of the function of the candidate genes. The major wood property QTL harbours a gene encoding a Cinnamoyl CoA reductase (CCR), a structural enzyme of the monolignol-specific biosynthesis pathway. Conclusions: Given the number of traits analysed, this study provides a comprehensive understanding of the genetic architecture of wood properties in this Eucalyptus full-sib pedigree. At the dawn of Eucalyptus genome sequence, it will provide a framework to identify the nature of genes underlying these important quantitative traits. (Résumé d'auteur

High-Level Expression of Wild-Type p53 in Melanoma Cells is Frequently Associated with Inactivity in p53 Reporter Gene Assays

Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Methodology/Principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5–8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. Conclusions/Significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level