A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men

Background Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD). Methods We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model. Results The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32–4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50–6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups. Conclusions To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of the RAS gene family in alcoholism and ALD

Behavioral and Endocrine Consequences of Simultaneous Exposure to Two Different Stressors in Rats: Interaction or Independence?

Although behavioral and endocrine consequences of acute exposure to stressors have been extensively studied, little is known about how simultaneous exposure to two different stressors interacts to induce short- and long-term effects. In the present experiment we studied this interaction in adult male rats exposed to cat fur odor (impregnated cloth) or immobilization on boards either separately or simultaneously. We reasoned that exposure to the odor of a potential predator while immobilized, may potentiate its negative consequences as compared to exposure to only one of the stressors. Exposure to cat odor elicited the expected reduction of activity and avoidance of the area where the impregnated cloth was located. The endocrine response (plasma levels of ACTH and corticosterone, as a measure of the hypothalamic-pituitary-adrenal axis, HPA) was markedly greater after immobilization than after cat fur odor and no additive effects were found by simultaneous exposure to both stressors. Cat odor, but not immobilization, increased anxiety-like behavior as evaluated in the elevated plus-maze 7 days after the stressors, with no evidence of enhanced HPA activation. In addition, cat odor exposure resulted in long-lasting (8 days later) fear conditioning to the box containing a clean cloth, which was reflected by hypoactivity, avoidance of the cloth area and enhanced HPA activation. All these effects were similarly observed in rats exposed simultaneously to cat odor and immobilization. In rats only exposed to immobilization, only some weak behavioral signs of fear conditioning were found, but HPA activation in response to the context paired to immobilization was enhanced to the same extent as in cat odor-exposed animals, supporting a certain degree of endocrine conditioning. The present results did not reveal important behavioral interactions between the two stressors when animals experienced both simultaneously, whereas some interactions were found regarding HPA activation. Theoretical implications are discussed

The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala

In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medial ganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novel model of the neuronal composition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.This work was supported by Grants of the French National Research Agency (Agence Nationale de la Recherche; ANR) [ANR-13-BSV4-0011] and by the French Government through the ‘Investments for the Future’ LABEX SIGNALIFE [ANR-11-LABX-0028-01] to M.S., by the Spanish Government (BFU2007-60263 and BFU2010-17305) to A.F, and by the Medical Research Council (MR/K013750/1) to T.T. N.R.-R. is funded by a postdoctoral fellowship from the Ville de Nice, France (“Aide Individuelle aux Jeunes Chercheurs 2016”).Peer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

First measurement of the Z→μ+μ− angular coefficients in the forward region of pp collisions at √s = 13 TeV

The first study of the angular distribution of μ + μ − pairs produced in the forward rapidity region via the Drell-Yan reaction p p → γ ∗ / Z + X → ℓ + ℓ − + X is presented, using data collected with the LHCb detector at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 5.1     fb − 1 . The coefficients of the five leading terms in the angular distribution are determined as a function of the dimuon transverse momentum and rapidity. The results are compared to various theoretical predictions of the Z -boson production mechanism and can also be used to probe transverse-momentum-dependent parton distributions within the proton

Search for Lepton-Universality Violation in B^{+}→K^{+}ℓ^{+}ℓ^{-} Decays.

A measurement of the ratio of branching fractions of the decays B^{+}→K^{+}μ^{+}μ^{-} and B^{+}→K^{+}e^{+}e^{-} is presented. The proton-proton collision data used correspond to an integrated luminosity of 5.0  fb^{-1} recorded with the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. For the dilepton mass-squared range 1.1<q^{2}<6.0  GeV^{2}/c^{4} the ratio of branching fractions is measured to be R_{K}=0.846_{-0.054}^{+0.060}_{-0.014}^{+0.016}, where the first uncertainty is statistical and the second systematic. This is the most precise measurement of R_{K} to date and is compatible with the standard model at the level of 2.5 standard deviations

Evidence for an η c ( 1 S ) π - resonance in B 0 → η c ( 1 S ) K + π - decays.

A Dalitz plot analysis of B 0 → η c ( 1 S ) K + π - decays is performed using data samples of pp collisions collected with the LHCb detector at centre-of-mass energies of s = 7 , 8 and 13 Te V , corresponding to a total integrated luminosity of 4.7 fb - 1 . A satisfactory description of the data is obtained when including a contribution representing an exotic η c ( 1 S ) π - resonant state. The significance of this exotic resonance is more than three standard deviations, while its mass and width are 4096 ± 20 - 22 + 18 Me V and 152 ± 58 - 35 + 60 Me V , respectively. The spin-parity assignments J P = 0 + and J P = 1 - are both consistent with the data. In addition, the first measurement of the B 0 → η c ( 1 S ) K + π - branching fraction is performed and gives B ( B 0 → η c ( 1 S ) K + π - ) = ( 5.73 ± 0.24 ± 0.13 ± 0.66 ) × 10 - 4 , where the first uncertainty is statistical, the second systematic, and the third is due to limited knowledge of external branching fractions

Study of the ψ2(3823)ψ_2(3823) and χc1(3872)χ_{c1}(3872) states in B+→(Jψπ+π−)K+B^+ \rightarrow \left( Jψπ^+π^-\right)K^+ decays

The decays $B^+\rightarrow J/\psi \pi^+ \pi^- K^+$ are studied using a data set corresponding to an integrated luminosity of 9fb$^{-1}$ collected with the LHCb detector in proton-proton collisions between 2011 and 2018. Precise measurements of the ratios of branching fractions with the intermediate $\psi_2(3823)$, $\chi_{c1}(3872)$ and $\psi(2S)$ states are reported. The decay of $B^+\rightarrow \psi_2(3823)K^+$ with $\psi_2(3823)\rightarrow J\psi\pi^+\pi^-$ is observed for the first time with a significance of 5.1 standard deviations. The mass differences between the $\psi_2(3823)$, $\chi_{c1}(3872)$ and $\psi(2S)$ states are measured to be $$\begin{array}{rcl} m_{\chi_{c1(3872)}} - m_{\psi_2(3823)} &= & 47.50 \pm 0.53 \pm 0.13\,\mathrm{MeV/}c^2\,, \\ m_{\psi_2(3823)} - m_{\psi(2S)} &= & 137.98 \pm 0.53 \pm 0.14\,\mathrm{MeV/}c^2\,, \\ m_{\chi_{c1}(3872)} - m_{\psi(2S)} &= & 185.49 \pm 0.06 \pm 0.03\,\mathrm{MeV/}c^2\,, \end{array}$$ resulting in the most precise determination of the $\chi_{c1}(3782)$ mass. The width of the $\psi_2(3823)$ state is found to be below 5.2MeV at 90\% confidence level. The Breit-Wigner width of the $\chi_{c1}(3872)$ state is measured to be $$\Gamma^{\mathrm{BW}}_{\chi_{c1}(3872)} = 0.96^{+0.19}_{-0.18}\pm0.21 \mathrm{MeV},$$ which is inconsistent with zero by 5.5 standard deviations

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified