Implementation of laparoscopic hysterectomy for endometrial cancer over the past decade

Background: Laparoscopic hysterectomy (LH) for the treatment of early-stage endometrial carcinoma/cancer (EC) has demonstrated to be safe in several randomized controlled trials. Yet, data on implementation of LH in clinical practice are limited. In the present study, implementation of LH for EC was evaluated in a large oncology network in the Netherlands. Results: Retrospectively, a total of 556 EC patients with FIGO stage I-II were registered in the selected years. The proportion of LH gradually increased from 11% in 2006 to 85% in 2015. LH was more often performed in patients with low-grade EC and was not related to the studied patient characteristics. The introduction of TLH was frequently preceded by LAVH. Patients treated in teaching hospitals were more likely to undergo a LH compared to patients in non-teaching hospitals. The conversion rate was 7.7%, and the overall complication rates between LH and AH were comparable, but less postoperative complications in LH. Conclusions: Implementation of laparoscopic hysterectomy for early-stage EC increased from 11 to 85% in 10 years. Implementation of TLH was often preceded by LAVH and was faster in teaching hospitals

Contribution of limbic norepinephrine to cannabinoid-induced aversion

RATIONALE: The cannabinoid system has risen to the forefront in the development of novel treatments for a number of pathophysiological processes. However, significant side effects have been observed in clinical trials raising concerns regarding the potential clinical utility of cannabinoid-based agents. Understanding the neural circuits and neurochemical substrates impacted by cannabinoids will provide a better means of gaging their actions within the central nervous system that may contribute to the expression of unwanted side effects. OBJECTIVES: In the present study, we investigated whether norepinephrine (NE) in the limbic forebrain is a critical determinant of cannabinoid receptor agonist-induced aversion and anxiety in rats. METHODS: An immunotoxin lesion approach was combined with behavioral analysis using a place conditioning paradigm and the elevated zero maze. RESULTS: Our results show that the non-selective CB1/CB2 receptor agonist, WIN 55,212-2, produced a significant place aversion in rats. Further, NE in the nucleus accumbens was critical for WIN 55,212-2-induced aversion but did not affect anxiety-like behaviors. Depletion of NE from the bed nucleus of the stria terminalis was ineffective in altering WIN 55,212-2-induced aversion and anxiety. CONCLUSIONS: These results indicate that limbic, specifically accumbal, NE is required for cannabinoid-induced aversion but is not essential to cannabinoid-induced anxiety.This works was supported by PHS grant DA 020129. Ana Franky Carvalho was supported by the Portuguese Foundation for Science and Technology (SFRH/BD/33236/2007)

Identification of Keratinocyte Growth Factor as a Target of microRNA-155 in Lung Fibroblasts: Implication in Epithelial-Mesenchymal Interactions

International audienceBACKGROUND: Epithelial-mesenchymal interactions are critical in regulating many aspects of vertebrate embryo development, and for the maintenance of homeostatic equilibrium in adult tissues. The interactions between epithelium and mesenchyme are believed to be mediated by paracrine signals such as cytokines and extracellular matrix components secreted from fibroblasts that affect adjacent epithelia. In this study, we sought to identify the repertoire of microRNAs (miRNAs) in normal lung human fibroblasts and their potential regulation by the cytokines TNF-alpha, IL-1beta and TGF-beta. METHODOLOGY/PRINCIPAL FINDINGS: MiR-155 was significantly induced by inflammatory cytokines TNF-alpha and IL-1beta while it was down-regulated by TGF-beta. Ectopic expression of miR-155 in human fibroblasts induced modulation of a large set of genes related to "cell to cell signalling", "cell morphology" and "cellular movement". This was consistent with an induction of caspase-3 activity and with an increase in cell migration in fibroblasts tranfected with miR-155. Using different miRNA bioinformatic target prediction tools, we found a specific enrichment for miR-155 predicted targets among the population of down-regulated transcripts. Among fibroblast-selective targets, one interesting hit was keratinocyte growth factor (KGF, FGF-7), a member of the fibroblast growth factor (FGF) family, which owns two potential binding sites for miR-155 in its 3'-UTR. Luciferase assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Site-directed mutagenesis revealed that only one out of the 2 potential sites was truly functional. Functional in vitro assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Furthermore, in vivo experiments using a mouse model of lung fibrosis showed that miR-155 expression level was correlated with the degree of lung fibrosis. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest a physiological function of miR-155 in lung fibroblasts. Altogether, this study implicates this miRNA in the regulation by mesenchymal cells of surrounding lung epithelium, making it a potential key player during tissue injury

Deskundigenpanel: demografische gevolgen emancipatiebeleid beperkt

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Cannabinoid modulation of noradrenergic circuits: Implications for psychiatric disorders

The interaction between the endocannabinoid system and catecholaminergic circuits has gained increasing attention as it is recognized that the development of synthetic cannabinoid receptor agonists/antagonists or compounds targeting endocannabinoid synthesis/metabolism may hold some therapeutic potential for the treatment of psychiatric disorders. The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Recent evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. This review summarizes our current knowledge regarding the anatomical substrates underlying regulation of noradrenergic circuitry by the endocannabinoid system. It then presents biochemical evidence showing an important effect of cannabinoid modulation on adrenergic receptor signaling. Finally, new evidence from behavioral pharmacology studies is provided demonstrating that norepinephrine is a critical determinant of cannabinoid-induced aversion, adding another dimension to how central noradrenergic circuitry is regulated by the cannabinoid systemGrant support: NIDA DA020129

Evidence of a J/ψΛJ/\psi\Lambda structure and observation of excited Ξ−\Xi^- states in the Ξb−→J/ψΛK−\Xi^-_b \to J/\psi\Lambda K^- decay

First evidence of a structure in the $J/\psi{\Lambda}$ invariant mass distribution is obtained from an amplitude analysis of $\Xi_b^-{\rightarrow}J/\psi{\Lambda}K^-$ decays. The observed structure is consistent with being due to a charmonium pentaquark with strangeness with a significance of $3.1\sigma$ including systematic uncertainties and look-elsewhere effect. Its mass and width are determined to be $4458.8\pm2.9^{+4.7}_{-1.1}$ MeV and $17.3\pm6.5^{+8.0}_{-5.7}$ MeV, respectively, where the quoted uncertainties are statistical and systematic. The structure is also consistent with being due to two resonances. In addition, the narrow excited $\Xi^-$ states, $\Xi(1690)^-$ and $\Xi(1820)^-$, are seen for the first time in a $\Xi^-_b$ decay, and their masses and widths are measured with improved precision. The analysis is performed using $pp$ collision data corresponding to a total integrated luminosity of 9 fb$^{-1}$, collected with the LHCb experiment at centre-of-mass energies of 7, 8 and 13 TeV

Measurement of CP asymmetries in D(s)+→ηπ+ {D}_{(s)}^{+}\to \eta {\pi}^{+} and D(s)+→η′π+ {D}_{(s)}^{+}\to {\eta}^{\prime }{\pi}^{+} decays

Searches for CP violation in the decays ${D}_{(s)}^{+}\to \eta {\pi}^{+}$ and ${D}_{(s)}^{+}\to {\eta}^{\prime }{\pi}^{+}$ are performed using pp collision data corresponding to 6 fb$^{−1}$ of integrated luminosity collected by the LHCb experiment. The calibration channels ${D}_{(s)}^{+}\to \phi {\pi}^{+}$ are used to remove production and detection asymmetries. The resulting CP-violating asymmetries are${\displaystyle \begin{array}{l}{\mathcal{A}}^{CP}=\left({D}^{+}\to \eta {\pi}^{+}\right)=\left(0.34\pm 0.66\pm 0.16\pm 0.05\right)\%,\\ {}{\mathcal{A}}^{CP}=\left({D}_s^{+}\to \eta {\pi}^{+}\right)=\left(0.32\pm 0.51\pm 0.12\right)\%,\\ {}\begin{array}{l}{\mathcal{A}}^{CP}=\left({D}^{+}\to {\eta}^{\prime }{\pi}^{+}\right)=\left(0.49\pm 0.18\pm 0.06\pm 0.05\right)\%,\\ {}{\mathcal{A}}^{CP}=\left({D}_s^{+}\to {\eta}^{\prime }{\pi}^{+}\right)=\left(0.01\pm 0.12\pm 0.08\right)\%,\end{array}\end{array}}$where the first uncertainty is statistical, the second is systematic and the third, relevant for the D$^{+}$ channels, is due to the uncertainty on ${\mathcal{A}}^{CP}=\left({D}^{+}\to \phi {\pi}^{+}\right)$. These measurements, currently the most precise for three of the four channels considered, are consistent with the absence of CP violation. A combination of these results with previous LHCb measurements is presented.[graphic not available: see fulltext]Searches for $CP$ violation in the decays $D^+_{(s)}\rightarrow \eta \pi^+$ and $D^+_{(s)}\rightarrow \eta^{\prime} \pi^+$ are performed using $pp$ collision data corresponding to 6 fb$^{-1}$ of integrated luminosity collected by the LHCb experiment. The calibration channels $D^+_{(s)}\rightarrow \phi \pi^+$ are used to remove production and detection asymmetries. The resulting $CP$-violating asymmetries are $A^{CP}(D^+ \rightarrow \eta \pi^+) = (0.34 \pm 0.66 \pm 0.16 \pm 0.05)\%$, $A^{CP}(D^+_s \rightarrow \eta \pi^+) = (0.32 \pm 0.51 \pm 0.12)\%$, $A^{CP}(D^+ \rightarrow \eta^{\prime} \pi^+) = (0.49 \pm 0.18 \pm 0.06 \pm 0.05)\%$, $A^{CP}(D^+_s \rightarrow \eta^{\prime} \pi^+) = (0.01 \pm 0.12 \pm 0.08)\%$, where the first uncertainty is statistical, the second is systematic and the third, relevant for the $D^+$ channels, is due to the uncertainty on $A^{CP}(D^+ \to \phi \pi^+)$. These measurements, currently the most precise for three of the four channels considered, are consistent with the absence of $CP$ violation. A combination of these results with previous LHCb measurements is presented