No association between the common calcium-sensing receptor polymorphism rs1801725 and irritable bowel syndrome

Background The calcium-sensing receptor (CaSR) is a calcium (Ca2+) sensitive G protein-coupled receptor implicated in various biological processes. In particular, it regulates Ca2+/Mg2+- homeostasis and senses interstitial Ca2+ levels and thereby controls downstream signalling cascades. Due to its expression in the gut epithelium, the enteric nervous system and smooth muscles and its key function in regulation and coordination of muscular contraction and secretion, it represents an excellent candidate gene to be investigated in the pathophysiology of irritable bowel syndrome (IBS). Disturbed CaSR structure and function may impact gastrointestinal regulation of muscular contraction, neuronal excitation and secretion and consequently contribute to symptoms seen in IBS, such as disordered defecation as well as disturbed gut motility and visceral sensitivity. Methods We have therefore genotyped the functional CASR SNP rs1801725 in three case control samples from the UK, Belgium and the USA. Results Genotype frequencies showed no association in the three genotyped case–control samples, neither with IBS nor with IBS subtypes. Conclusions Although we could not associate the SNP to any of the established bowel symptom based IBS subtypes we cannot rule out association to altered Ca2+ levels and disturbed secretion and gut motility which were unfortunately not assessed in the patients genotyped. This underlines the necessity of a more detailed phenotyping of IBS patients and control individuals in future studies

Global management of a common, underrated surgical task during the COVID-19 pandemic. Gallstone disease. An international survery

Background: Since the Coronavirus disease-19(COVID-19) pandemic, the healthcare systems are reallocating their medical resources, with consequent narrowed access to elective surgery for benign conditions such as gallstone disease(GD). This survey represents an overview of the current policies regarding the surgical management of patients with GD during the COVID-19 pandemic. Methods: A Web-based survey was conducted among 36 Hepato-Prancreato-Biliary surgeons from 14 Countries. Through a 17-item questionnaire, participants were asked about the local management of patients with GD since the start of the COVID-19 pandemic. Results: The majority (n = 26,72.2%) of surgeons reported an alarming decrease in the cholecystectomy rate for GD since the start of the pandemic, regardless of the Country: 19(52.7%) didn't operate any GD, 7(19.4%) reduced their surgical activity by 50–75%, 10(27.8%) by 25–50%, 1(2.8%) maintained regular activity. Currently, only patients with GD complications are operated. Thirty-two (88.9%) participants expect these changes to last for at least 3 months. In 15(41.6%) Centers, patients are currently being screened for SARS-CoV-2 infection before cholecystectomy [in 10(27.8%) Centers only in the presence of suspected infection, in 5(13.9%) routinely]. The majority of surgeons (n = 29,80.6%) have adopted a laparoscopic approach as standard surgery, 5(13.9%) perform open cholecystectomy in patients with known/suspected SARS-CoV-2 infection, and 2(5.6%) in all patients. Conclusion: In the ongoing COVID-19 emergency, the surgical treatment of GD is postponed, resulting in a huge number of untreated patients who could develop severe morbidity. Updated guidelines and dedicated pathways for patients with benign disease awaiting elective surgery are mandatory to prevent further aggravation of the overloaded healthcare systems

Transplanted Human Amniotic Membrane-Derived Mesenchymal Stem Cells Ameliorate Carbon Tetrachloride-Induced Liver Cirrhosis in Mouse

BACKGROUND: Human amniotic membrane-derived mesenchymal stem cells (hAMCs) have the potential to reduce heart and lung fibrosis, but whether could reduce liver fibrosis remains largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: Hepatic cirrhosis model was established by infusion of CCl₄ (1 ml/kg body weight twice a week for 8 weeks) in immunocompetent C57Bl/6J mice. hAMCs, isolated from term delivered placenta, were infused into the spleen at 4 weeks after mice were challenged with CCl₄. Control mice received only saline infusion. Animals were sacrificed at 4 weeks post-transplantation. Blood analysis was performed to evaluate alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Histological analysis of the livers for fibrosis, hepatic stellate cells activation, hepatocyte apoptosis, proliferation and senescence were performed. The donor cell engraftment was assessed using immunofluorescence and polymerase chain reaction. The areas of hepatic fibrosis were reduced (6.2%±2.1 vs. control 9.6%±1.7, p<0.05) and liver function parameters (ALT 539.6±545.1 U/dl, AST 589.7±342.8 U/dl,vs. control ALT 139.1±138.3 U/dl, p<0.05 and AST 212.3±110.7 U/dl, p<0.01) were markedly ameliorated in the hAMCs group compared to control group. The transplantation of hAMCs into liver-fibrotic mice suppressed activation of hepatic stellate cells, decreased hepatocyte apoptosis and promoted liver regeneration. More interesting, hepatocyte senescence was depressed significantly in hAMCs group compared to control group. Immunofluorescence and polymerase chain reaction revealed that hAMCs engraftment into host livers and expressed the hepatocyte-specific markers, human albumin and α-fetoproteinran. CONCLUSIONS/SIGNIFICANCE: The transplantation of hAMCs significantly decreased the fibrosis formation and progression of CCl₄-induced cirrhosis, providing a new approach for the treatment of fibrotic liver disease

Localization and Functional Characterization of the Rat Oatp4c1 Transporter in an In Vitro Cell System and Rat Tissues

The organic anion transporting polypeptide 4c1 (Oatp4c1) was previously identified as a novel uptake transporter predominantly expressed at the basolateral membrane in the rat kidney proximal tubules. Its functional role was suggested to be a vectorial transport partner of an apically-expressed efflux transporter for the efficient translocation of physiological substrates into urine, some of which were suggested to be uremic toxins. However, our in vitro studies with MDCKII cells showed that upon transfection rat Oatp4c1 polarizes to the apical membrane. In this report, we validated the trafficking and function of Oatp4c1 in polarized cell systems as well as its subcellular localization in rat kidney. Using several complementary biochemical, molecular and proteomic methods as well as antibodies amenable to immunohistochemistry, immunofluorescence, and immunobloting we investigated the expression pattern of Oatp4c1 in polarized cell systems and in the rat kidney. Collectively, these data demonstrate that rat Oatp4c1 traffics to the apical cell surface of polarized epithelium and localizes primarily in the proximal straight tubules, the S3 fraction of the nephron. Drug uptake studies in Oatp4c1-overexpressing cells demonstrated that Oatp4c1-mediated estrone-3-sulfate (E3S) uptake was pH-dependent and ATP-independent. These data definitively demonstrate the subcellular localization and histological location of Oatp4c1 and provide additional functional evidence that reconciles expression-function reports found in the literature

Measurement of the muon flux at the SND@LHC experiment

The Scattering and Neutrino Detector at the LHC (SND@LHC) started taking data at the beginning of Run 3 of the LHC. The experiment is designed to perform measurements with neutrinos produced in proton-proton collisions at the LHC in an energy range between 100 GeV and 1 TeV. It covers a previously unexplored pseudo-rapidity range of 7.2 &lt; η&lt; 8.4 . The detector is located 480 m downstream of the ATLAS interaction point in the TI18 tunnel. It comprises a veto system, a target consisting of tungsten plates interleaved with nuclear emulsion and scintillating fiber (SciFi) trackers, followed by a muon detector (UpStream, US and DownStream, DS). In this article we report the measurement of the muon flux in three subdetectors: the emulsion, the SciFi trackers and the DownStream Muon detector. The muon flux per integrated luminosity through an 18 × 18 cm 2 area in the emulsion is: 1.5±0.1(stat)×104fb/cm2. The muon flux per integrated luminosity through a 31 × 31 cm 2 area in the centre of the SciFi is: 2.06±0.01(stat)±0.12(sys)×104fb/cm2 The muon flux per integrated luminosity through a 52 × 52 cm 2 area in the centre of the downstream muon system is: 2.35±0.01(stat)±0.10(sys)×104fb/cm2 The total relative uncertainty of the measurements by the electronic detectors is 6 % for the SciFi and 4 % for the DS measurement. The Monte Carlo simulation prediction of these fluxes is 20–25 % lower than the measured values

Results and Perspectives from the First Two Years of Neutrino Physics at the LHC by the SND@LHC Experiment

After rapid approval and installation, the SND@LHC Collaboration was able to gather data successfully in 2022 and 2023. Neutrino interactions from νμs originating at the LHC IP1 were observed. Since muons constitute the major background for neutrino interactions, the muon flux entering the acceptance was also measured. To improve the rejection power of the detector and to increase the fiducial volume, a third Veto plane was recently installed. The energy resolution of the calorimeter system was measured in a test beam. This will help with the identification of νe interactions that can be used to probe charm production in the pseudo-rapidity range of SND@LHC (7.2 < η < 8.4). Events with three outgoing muons have been observed and are being studied. With no vertex in the target, these events are very likely from muon trident production in the rock before the detector. Events with a vertex in the detector could be from trident production, photon conversion, or positron annihilation. To enhance SND@LHC’s physics case, an upgrade is planned for HL-LHC that will increase the statistics and reduce the systematics. The installation of a magnet will allow the separation of νμ from ν¯μWe acknowledge the support for the construction and operation of the SND@LHC detector provided by the following funding agencies: CERN; the Bulgarian Ministry of Education and Science within the National Roadmap for Research Infrastructures 2020–2027 (object CERN); ANID—Millennium Program—ICN2019_044 (Chile); the Deutsche Forschungsgemeinschaft (DFG, ID 496466340); the Italian National Institute for Nuclear Physics (INFN); JSPS, MEXT, the Global COE program of Nagoya University, the Promotion and Mutual Aid Corporation for Private Schools of Japan for Japan; the National Research Foundation of Korea with grant numbers 2021R1A2C2011003, 2020R1A2C1099546, 2021R1F1A1061717, and 2022R1A2C100505; Fundação para a Ciência e a Tecnologia, FCT (Portugal), CERN/FIS-INS/0028/2021; the Swiss National Science Foundation (SNSF); TENMAK for Turkey (Grant No. 2022TENMAK(CERN) A5.H3.F2-1). M. Climesu, H. Lacker and R. Wanke are funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Project 496466340. We acknowledge the funding of individuals by Fundação para a Ciência e a Tecnologia, FCT (Portugal) with grant numbers CEECIND/01334/2018, CEECINST/00032/2021 and PRT/BD/153351/2021.CERNBulgarian Ministry of Education and ScienceANID—Millennium ProgramDeutsche ForschungsgemeinschaftItalian National Institute for Nuclear Physics (INFN)JSPS, MEXT, the Global COE program of Nagoya University, the Promotion and Mutual Aid Corporation for Private Schools of Japan for JapanNational Research Foundation of KoreaFundação para a Ciência e a Tecnologia, FCT (Portugal)Swiss National Science Foundation (SNSF)TENMAK for TurkeyPeer Reviewe

Observation of Collider Muon Neutrinos with the SND@LHC Experiment

We report the direct observation of muon neutrino interactions with the SND@LHC detector at the Large Hadron Collider. A dataset of proton-proton collisions at s=13.6 TeV collected by SND@LHC in 2022 is used, corresponding to an integrated luminosity of 36.8 fb-1. The search is based on information from the active electronic components of the SND@LHC detector, which covers the pseudorapidity region of 7.2&lt;8.4, inaccessible to the other experiments at the collider. Muon neutrino candidates are identified through their charged-current interaction topology, with a track propagating through the entire length of the muon detector. After selection cuts, 8 νμ interaction candidate events remain with an estimated background of 0.086 events, yielding a significance of about 7 standard deviations for the observed νμ signal

Thinking about Eating Food Activates Visual Cortex with Reduced Bilateral Cerebellar Activation in Females with Anorexia Nervosa: An fMRI Study

Background: Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown. Methods: Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC). Results: Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions. Conclusions: These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes

Observation of Collider Muon Neutrinos with the SND@LHC Experiment

We report the direct observation of muon neutrino interactions with the SND@LHC detector at the Large Hadron Collider. A dataset of proton-proton collisions at √ s = 13.6 TeV collected by SND@LHC in 2022 is used, corresponding to an integrated luminosity of 36.8 fb − 1 . The search is based on information from the active electronic components of the SND@LHC detector, which covers the pseudorapidity region of 7.2 < η < 8.4 , inaccessible to the other experiments at the collider. Muon neutrino candidates are identified through their charged-current interaction topology, with a track propagating through the entire length of the muon detector. After selection cuts, 8 ν μ interaction candidate events remain with an estimated background of 0.086 events, yielding a significance of about 7 standard deviations for the observed ν μ signal